Skip to main content
SpringerLink
Log in

Age-Related Changes Affecting Atherosclerotic Risk

Potential for Pharmacological Intervention

  • Review Article
  • Clinical Pharmacology
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

The incidence of cardiovascular diseases that are related to the atherosclerotic process increases exponentially with age. Organ lesions, the clinical manifestation of atherosclerotic disease, are late events due to complications in the plaque (ulceration, thrombosis, calcification) which are the result of an increased vulnerability to disruption of a previously stable plaque. The higher incidence of age-related clinical events could be explained by a rising sensitivity of plaques to destabilising factors, both parietal and humoral.

The increased probability that a plaque in an elderly patient will became vulnerable could be related to those destabilising factors that significantly increase with aging, such as advanced glycation end-products.

For these reasons, it seems most important that the analysis of these age-related destabilising factors, rather than those factors that promote the development of early atherosclerotic plaques, should be undertaken. Taking the point of view of a pharmacological intervention, this should eventually lead to a more complete understanding of this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Eggen DA, Solberg LA. Variation of atherosclerosis with age. Lab Invest 1968; 18: 571–9

    PubMed  CAS  Google Scholar 

  2. Bierman EL, Ross R. Aging and atherosclerosis. In: Paoletti R, Gotto AM, editors. Atherosclerosis reviews. Vol. 2. New York: Raven Press, 1977: 79–111

    Google Scholar 

  3. Stary HC. Evolution and progression of atherosclerosis in the coronary arteries of children and adults. In: Bates SR, Gangloff EC, editors. Atherogenesis and aging. New York: Springer-Verlag, 1987: 20–36

    Google Scholar 

  4. Simons LA. Epidemiologic considerations in cardiovascular diseases in the elderly: international comparison and trends. Am J Cardiol 1989; 63: 5H–8H

    PubMed  CAS  Google Scholar 

  5. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801–9

    PubMed  CAS  Google Scholar 

  6. Faxon DP, Sanborn TA, Haudenschild CC, et al. Restenosis following transluminal coronary angioplasty in experimental atherosclerosis. Arteriosclerosis 1984; 4: 189–95

    PubMed  CAS  Google Scholar 

  7. Haudenschild CC. Pathogenesis of atherosclerosis: state of the art. Cardiovasc Drugs Ther 1990; 4: 993–1004

    PubMed  Google Scholar 

  8. Schwartz RS, Holmes DR, Topol EJ. The restenosis paradigm revisited: an alternative proposal for cellular mechanism. J Am Coll Cardiol 1992; 20: 1284–93

    PubMed  CAS  Google Scholar 

  9. McGill Jr CH, Geer JC, Strong JP. Natural history of human atherosclerotic lesions. In: Sandler M, Bourne GH, editors. Atherosclerosis and its origin. New York: Academic Press, 1963: 39–65

    Google Scholar 

  10. Haust MD. The natural history of human atherosclerotic lesions. In: Moore S, editor. Vascular injury and atherosclerosis. New York: Marcel Dekker, 1981: 1–24

    Google Scholar 

  11. Spagnoli LG. Rise and regression of the human fibro-atheromatous plaque (natural history and morphology) [in Italian]. G Arterioscler 1983; 8: 117–45

    Google Scholar 

  12. Muller JE, Tofler GH, Stone PH. Circadian variation and triggers of onset of acute cardiovascular disease. Circulation 1989; 79: 733–43

    PubMed  CAS  Google Scholar 

  13. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92: 657–71

    PubMed  CAS  Google Scholar 

  14. Pacifici RE, Davies KJ. Protein, lipid and DNA repair systems in oxidative stress: the free-radical theory of aging revisited. Gerontology 1991; 37: 166–80

    PubMed  CAS  Google Scholar 

  15. Nohl H. Involvement of free radicals in ageing: a consequence or cause of senescence. Br Med Bull 1993; 49: 653–67

    PubMed  CAS  Google Scholar 

  16. Bucala R, Cerani A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 1992; 23: 1–34

    PubMed  CAS  Google Scholar 

  17. Holmes GE, Bernstein C, Bernstein H. Oxidative and DNA damage as the basis of aging: a review. Mutat Res 1992; 275: 305–15

    PubMed  CAS  Google Scholar 

  18. Stemerman MB, Weinstein R, Rowe JW, et al. Vascular smooth muscle cell growth kinetics in vivo in aged rats. Proc Natl Acad Sci USA 1982; 79: 3863–6

    PubMed  CAS  Google Scholar 

  19. Spagnoli LG, Sambuy Y, Palmieri G, et al. Age-related modulation of vascular smooth muscle cells proliferation following arterial wall damage. Artery 1985; 13: 187–98

    PubMed  CAS  Google Scholar 

  20. Bochaton-Piallat ML, Gabbiani F, Ropraz P, et al. Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones. Arterioscler Thromb 1993; 13: 1449–55

    PubMed  CAS  Google Scholar 

  21. Dobrin PB. Mechanical properties of arteries. Phys Rev 1978; 58: 397–421

    CAS  Google Scholar 

  22. Movat ZH, More MH, Haust MD. The diffuse intimai thickening of human aorta with aging. Am J Pathol 1958; 34: 1023–35

    PubMed  CAS  Google Scholar 

  23. Tracy RE, Strong JP, Toca VT, et al. Variable patterns of non-atheromatous aortic intimai thickening. Lab Invest 1979; 41: 553–9

    PubMed  CAS  Google Scholar 

  24. Scebat L, Renais J, Hadjisky P. Histometabolic and structural changes during arterial wall ageing. Possible role of immune process. In: Cavallero C, editor. The arterial wall in atherogenesis. Padova: Piccin Medical Book, 1975: 43–60

    Google Scholar 

  25. Spagnoli LG, Orlandi A, Mauriello A, et al. Aging and atherosclerosis in the rabbit: 1. Distribution, prevalence and morphology of atherosclerotic lesions. Atherosclerosis 1991; 89: 11–24

    PubMed  CAS  Google Scholar 

  26. Haust MD. The morphogenesis and fate of potential and early atherosclerotic lesions in man. Human Pathol 1971; 2: 1–13

    CAS  Google Scholar 

  27. Stary HC. Macrophages, macrophage foam cells, and eccentric intimai thickening in the coronary arteries of young children. Atherosclerosis 1987; 64: 91–108

    PubMed  CAS  Google Scholar 

  28. Spagnoli LG, Orlandi A, Mauriello A, et al. Age-dependent increase of rabbit aortic wall sensitivity to atherosclerosis: a morphometric approach. Pathol Res Pract 1992; 4–5: 637–42

    Google Scholar 

  29. Kritchevsky D. Diet, lipid, metabolism, and aging. Fed Proc 1979; 38: 2001–6

    PubMed  CAS  Google Scholar 

  30. Dietschy JM. The effect of aging on the processes that regulates plasma LDL cholesterol levels in animals and man. In: Bates SR, Gangloff EC, editors. Atherosclerosis and aging. New York: Springer Verlag, 1987: 104–22

    Google Scholar 

  31. Elliot RJ, McGrath LT. Calcification of the human thoracic aorta during aging. Calcif Tissue Int 1994; 54: 268–73

    Google Scholar 

  32. Blankenhorn DH. Coronary calcification: a review. Am J Med Sci 1961; 242: 1–9

    Google Scholar 

  33. Kragel AH, Reddy SG, Wittes JT, et al. Morphometric analysis of the composition of atherosclerotic plaques in four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death. Circulation 1989; 80: 1747–56

    PubMed  CAS  Google Scholar 

  34. Ettinger WH. Lipid levels and risk of atherosclerotic coronary heart disease in the older person. Med Clin North Am 1989; 73: 1525–30

    PubMed  CAS  Google Scholar 

  35. Abbott RD, Garrison RJ, Wilson PWF, et al. Joint distribution of lipoprotein cholesterol classes. The Framingham Study. Arteriosclerosis 1983; 3: 260–72

    PubMed  CAS  Google Scholar 

  36. Gordon T, Castelli WP, Hjortland MC. High-density lipoprotein as a protective effect against coronary heart disease: the Framingham Study. Am J Med 1977; 62: 707–16

    PubMed  CAS  Google Scholar 

  37. Hainer NS, Kjelsberg MO, Epstein FH, et al. Carbohydrate tolerance and diabetes in a total community, Tecumseth, Michigan. Diabetes 1965; 14: 413–9

    Google Scholar 

  38. Health and Public Policy Committee, American College of Physicians. Bone mineral densitometry. Ann Intern Med 1987; 107: 932–40

    Google Scholar 

  39. Kannel WB, LeBauer EJ, Dawber TR, et al. Relation of body weight to development of coronary heart disease: the Framingham Study. Circulation 1967; 35: 734–44

    PubMed  CAS  Google Scholar 

  40. Matsuda T. Antithrombotic drugs. Nippon Ronen Igakkai Zasshi 1989; 26: 124–30

    PubMed  CAS  Google Scholar 

  41. Kannel WP, Castelli WP, Gordon T, et al. Serum cholesterol lipoprotein and the risk of coronary heart disease. Ann Intern Med 1973; 74: 1–31

    Google Scholar 

  42. Gotto AM, Gorry GA, Thompson JR, et al. Relationship between plasma lipid concentration and coronary artery disease in 496 patients. Circulation 1977; 56: 875–83

    PubMed  CAS  Google Scholar 

  43. Rose G, Shipley M. Plasma cholesterol concentration and death from coronary heart disease: 10 year results of the Whitehall study. BMJ 1986; 293: 306–7

    PubMed  CAS  Google Scholar 

  44. Castelli WP, Peter WF, Wilson MD, et al. Cardiovascular risk factors in the elderly. Am J Cardiol 1989; 63: 12H–9H

    PubMed  CAS  Google Scholar 

  45. Zimetbaum P, Frishman W, Aronson M. Lipids, vascular disease, and dementia with advancing age: epidemiologic considerations. Arch Intern Med 1991; 151: 240–4

    PubMed  CAS  Google Scholar 

  46. Epstein FH, Francis TJ, Hayner NS, et al. Prevalence of chronic disease and distribution of selected physiological variables in a total community. Tecumseh, Michigan. Am J Epidemiol 1965; 81: 307–22

    PubMed  CAS  Google Scholar 

  47. Woolf N. Morphological changes in atherosclerosis and the effects of hyperlipidemia on the artery wall. In: Stokes J, Mancini M, editors. Atherosclerosis reviews. Vol. 18. New York: Raven Press Ltd, 1988: 25–48

    Google Scholar 

  48. Finch CE, Schneider EL, editors. Handbook of the biology of aging, 2th ed. New York: Van Nostrand Reinhold Co, 1985

    Google Scholar 

  49. Rouser G, Solomon LD. Changes in phospholipid composition of human aorta with age. Lipids 1969; 4: 232–4

    PubMed  CAS  Google Scholar 

  50. Eisemberg S, Stein Y, Stein O. Phospholipases in arterial tissue. Phosphatide acyl-hydrolase, lysophosphatide acyl-hydrolase and sphingomyelin choline phosphohydrolase in rat and rabbit aorta in different age groups. Biochim Biophys Acta 1969; 176: 557–63

    Google Scholar 

  51. Eriksson H, Carson LA. Quantitative and qualitative serum lipoprotein in analyses in healthy men compared with male myocardial infarctions and intermittent claudication. In: Settler G, Wizel A, editors. Atherosclerosis III: Proceedings of the Third International Symposium. Berlin: Springer Verlag, 1973: 838–9

    Google Scholar 

  52. Miller NE. Why does plasma low density lipoprotein concentration in adults increase with age? Lancet 1984; 1: 263–6

    PubMed  CAS  Google Scholar 

  53. Miller NE, La Ville A, Crook D. Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit. Nature 1985; 314: 109–11

    PubMed  CAS  Google Scholar 

  54. Badimon JJ, Badimon L, Galvez A, et al. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits. Lab Invest 1989; 60: 455–61

    PubMed  CAS  Google Scholar 

  55. Saku K, Gartside PS, Hynd BA, et al. Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest 1985; 75: 1702–12

    PubMed  CAS  Google Scholar 

  56. Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb 1991; 11: 2–14

    PubMed  CAS  Google Scholar 

  57. Gianturco SH, Bradley WA. Triglyceride-rich lipoproteins and their role in atherogenesis. Curr Opin Lipidol 1991; 2: 324–8

    CAS  Google Scholar 

  58. Gianturco SH, Gotto Jr AM, Jackson RL, et al. Control of 3-hydroxy-3-methylglutaryl-coA reductase activity in cultured human fibroblasts by hypertriglyceridemic very low density lipoproteins of subjects with hypertriglyceridemia. J Clin Invest 1978; 61: 320–8

    PubMed  CAS  Google Scholar 

  59. Agidir F, Marquie G. Effects preventifs du NN-dimethyl-biguanide sur le development de l’atherosclerose induite chez le lapin. CR Acad Sci (III) 1969; 269: 1000–11

    Google Scholar 

  60. Olsson AG, Ruhn G, Erikson U. The effect of serum lipid regulation on the development of femoral atherosclerosis in hyperlipidemia. A non-randomized controlled study. J Int Med 1990; 227: 381–90

    CAS  Google Scholar 

  61. Huttunen JK, Enholm C, Kekki M, et al. Post-heparin lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridemia: correlation to sex, age and various patterns of triglyceride metabolism. Clin Sci Mol Med 1976; 50: 249–56

    PubMed  CAS  Google Scholar 

  62. Master AM, Lasser RP, Jaffee HL. Blood pressure in white people over 65 years of age. Ann Intern Med 1958; 48: 284–90

    PubMed  CAS  Google Scholar 

  63. Subcommittee on Definition and Prevalence of the 1984 Joint National Committee. Hypertension prevalence and the status of awareness, treatment, and control in the United States. Hypertension 1985; 6: 457–68

    Google Scholar 

  64. Weber MA, Neutel JM, Cheung DG. Hypertension in the aged: a pathophysiologic basis for the treatment. Am J Cardiol 1989; 63: 25H–35H

    PubMed  CAS  Google Scholar 

  65. Johnson BC, Epstein FH, Kjelsberg MO. Distributions and familiar studies of blood pressure and serum cholesterol levels in a total community. Tecumseh, Michigan. J Chronic Dis 1965; 18: 147–57

    PubMed  CAS  Google Scholar 

  66. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA 1991; 265: 3255–64

    Google Scholar 

  67. Herd JA, Wood AJ, Blumenthal J, et al. Medical therapy in the elderly. J Am Coll Cardiol 1987; 10: 29A–34A

    PubMed  CAS  Google Scholar 

  68. Ostrander Jr LD, Neff BJ, Block WD, et al. Hyperglycemia and hypertriglyceridemia among persons with coronary heart disease. Ann Intern Med 1967; 67: 34–41

    PubMed  CAS  Google Scholar 

  69. Goldberg AP, Coon PJ. Non-insulin-dependent diabetes mellitus in the elderly. Influence of obesity and physical inactivity. Endocrinol Metab Clin North Am 1987; 16: 843–65

    PubMed  CAS  Google Scholar 

  70. Singer DE, Nathan DM, Anderson KM, et al. Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham study. Diabetes 1992; 41: 202–9

    PubMed  CAS  Google Scholar 

  71. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end-products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988; 318: 1315–21

    PubMed  CAS  Google Scholar 

  72. Hazzard WR. Biological basis of the sex differential in longevity. J Am Geriatr Soc 1986; 34: 455–71

    PubMed  CAS  Google Scholar 

  73. Hazzard WR. Atherosclerosis and aging: a scenario in flux. Am J Cardiol 1989; 63: 20H–4H

    PubMed  CAS  Google Scholar 

  74. Goodsland IF, Wynn V, Crook D, et al. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions. Am Heart J 1987; 114: 1467–503

    Google Scholar 

  75. Kannel W, editor. The Framingham Heart Study. Section 34. NIH Publication, 1987; no. 87-2703

  76. Esposito C, Gerlach H, Brett J, et al. Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med 1989; 170: 1387–407

    PubMed  CAS  Google Scholar 

  77. Spina M, Garbisa S, Hinnie J, et al. Age-related changes in composition and mechanical properties of tunica media of the upper thoracic human aorta. Arteriosclerosis 1983; 3: 64–76

    PubMed  CAS  Google Scholar 

  78. Gan JC, Murthy N, Nichols Jr CW, et al. Mucosubstances in the chicken aorta. Part 1. Changes with age in acid mucopolysaccharides, glycoproteins, collagen and elastin. J Atheroscler Res 1967; 7: 629–45

    PubMed  CAS  Google Scholar 

  79. Robert L, Jakob MP, Frances C, et al. Interaction between elastin and elastases and its role in the aging of the arterial wall, skin and other connective tissue: a review. Mech Ageing Dev 1984; 28: 155–66

    PubMed  CAS  Google Scholar 

  80. Mauriello A, Orlandi A, Oberholzer M, et al. Age-related morphological and morphometrical changes in rabbit aorta. Clin Ter Cardiovasc 1989; VIII: 265–8

    Google Scholar 

  81. Orlandi A, Mauriello M, Marino B, et al. Age-related modifications of aorta and coronaries in the rabbit: a morphological and morphometrical assessment. Arch Gerontol Ger 1993; 17: 37–53

    CAS  Google Scholar 

  82. Geer JC, Haust MD. Smooth muscle cells in atherosclerosis. Monographs on Atherosclerosis. Vol. 2. Basel: Karger, 1972

    Google Scholar 

  83. Friedman MH. A biologically plausible model of thickening of arterial intima under shear. Arteriosclerosis 1989; 9: 511–22

    PubMed  CAS  Google Scholar 

  84. Glagov S, Zarins CK. Is intimai hyperplasia an adaptive response or a pathologic process? Observations on the nature of nonatherosclerotic intimai thickening. J Vasc Surg 1989: 10; 571–3

    Google Scholar 

  85. Yoshida Y, Suzuki K, Shinkai H, et al. Morphological studies on age changes of arterial walls and progression of atherosclerosis in human aorta and cerebral arteries and effects of lipoproteins on proliferation on monkey aortic smooth muscle cells. Jpn Circ J 1980; 44: 13–32

    PubMed  CAS  Google Scholar 

  86. Wolinsky H. Long-term effects of hypertension on the rat aortic wall and their relation to concurrent aging changes. Circ Res 1972; 30: 301–9

    PubMed  CAS  Google Scholar 

  87. Faggioto A, Ross R, Harker L. Studies of hypercholesterolemia in the nonhuman primates. I. Changes that led to fatty streak formation. Arteriosclerosis 1984; 4: 323–40

    Google Scholar 

  88. Nakamura H, Izumiyama N, Nakamura K, et al. Age-associated ultrastructural changes in the aortic intima of rats with diet-induced hypercholesterolemia. Atherosclerosis 1989; 79: 101–11

    PubMed  CAS  Google Scholar 

  89. Cliff WJ. The aortic tunica media in aging rats. Exp Mol Pathol 1970; 13: 172–89

    PubMed  CAS  Google Scholar 

  90. Mauriello A, Oberholzer M, Orlandi A, et al. Age-related modification of average volume and anisotropy of vascular smooth muscle cells. Path Res Pract 1992; 188: 630–6

    PubMed  CAS  Google Scholar 

  91. Nejjar I, Pieraggi MT, Thiers JC, et al. Age-related changes in the elastic tissue of the human thoracic aorta. Atherosclerosis 1990; 80: 199–208

    PubMed  CAS  Google Scholar 

  92. John R, Thomas J. Chemical composition of elastins isolated from aortas and pulmonary tissue of humans of different ages. BiochemJ 1972; 127: 261–6

    CAS  Google Scholar 

  93. Spina M, Garbin G. Age related chemical changes in human elastins from non atherosclerotic areas of thoracic aorta. Atherosclerosis 1976; 24: 267–83

    PubMed  CAS  Google Scholar 

  94. Nakamura T, Tokita K, Tateno S, et al. Human aortic acid mucopolysaccharides and glycoprotein. Changes during ageing and the atherosclerosis. J Atheroscl Res 1968; 8: 891–902

    CAS  Google Scholar 

  95. Wight TR, Ross R. Proteoglycans in primate arteries. Ultra structural localization and distribution in the intima. J Cell Biol 1975; 667: 660–75

    Google Scholar 

  96. Kumar V, Berenson GS, Ruiz M, et al. Acid mucopolysaccarides of human aorta. Part 1: variation with maturation. J Atheroscler Res 1967; 7: 573–83

    PubMed  CAS  Google Scholar 

  97. Porreca E, Ciccarelli R, Di Febbo C, et al. Protein kinase C pathway and proliferative responses of aged and young rat vascular smooth muscle cells. Atherosclerosis 1993; 104: 137–45

    PubMed  CAS  Google Scholar 

  98. McCaffrey TA, Falcone DJ. Evidence for an age-related dysfunction in the antiproliferative response to transforming growth factor-beta in vascular smooth muscle cells. Mol Biol Cell 1993; 4: 315–22

    PubMed  CAS  Google Scholar 

  99. Bobik A, Campbell JH. Vascular derived growth factors: cell biology, pathophysiology and pharmacology. Pharmacol Res 1993; 45: 1–42

    CAS  Google Scholar 

  100. McCaffrey T, Nicholson AC, Szabo PE, et al. Aging and arteriosclerosis. The increased proliferation or arterial smooth muscle cells isolated from old rats is associated with increased platelet-derived growth factor-like activity. J Exp Med 1988; 167: 163–74

    PubMed  CAS  Google Scholar 

  101. Chamley-Campbell JG, Campbell GR, Ross R. Smooth muscle cells in culture. Physiol Rev 1979; 59: 1–61

    PubMed  CAS  Google Scholar 

  102. Orlandi A, Ehrlich HP, Ropraz P, et al. Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro. Arterioscler Thromb 1994; 14: 982–9

    PubMed  CAS  Google Scholar 

  103. Orlandi A, Ropraz P, Gabbiani G. Proliferative activity and α-smooth muscle actin expression in cultured rat aortic smooth muscle cells are differently modulated by transforming growth factor βl and heparin. Exp Cell Res 1994; 214: 528–36

    PubMed  CAS  Google Scholar 

  104. Clarkson TB, Lofland HB, Bullock BC, et al. Atherosclerosis in some species of new world monkeys. Ann NY Acad Sci 1969; 162: 103–9

    PubMed  CAS  Google Scholar 

  105. Chobanian AV. The arterial smooth muscle cell in systemic hypertension. Am J Cardiol. 1987; 60: 941–81

    Google Scholar 

  106. Luscher TF, Tanner FC, Dohi Y. Age, hypertension and hypercholesterolemia alter endothelium-dependent vascular regulation. Pharmacol Toxicol 1992; 70: S32–9

    PubMed  CAS  Google Scholar 

  107. Rokitansky C. A manual of pathological anatomy. Vol 4. Berlin: Sydenham Society, 1852: 261–89

    Google Scholar 

  108. Hayashi K, Takamizawa K, Nakamura T, et al. Effects of elastase on the stiffness and elastic properties of arterial walls in cholesterol-fed rabbits. Atherosclerosis 1987; 66: 259–67

    PubMed  CAS  Google Scholar 

  109. Smith EB, Staples EM. Intimai and medial plasma protein concentrations and endothelial function. Atherosclerosis 1982; 41: 295–305

    PubMed  CAS  Google Scholar 

  110. Minick CR, Stemerman MB, Insull Jr W. Role of endothelium and hypercholesterolemia in intimai thickening and lipid accumulation. Am J Pathol 1979; 95: 131–40

    PubMed  CAS  Google Scholar 

  111. Londono I, LecIerc Y, Bendayan M. Ultrastructural localization of endogenous albumin in human aortic tissue by protein A-gold immunocytochemistry. Am J Pathol 1992; 140: 179–91

    PubMed  CAS  Google Scholar 

  112. Kurozumi T, Imamura T, Tanaka K, et al. Permeation and deposition of fibrinogen and low-density lipoprotein in the aorta and cerebral artery of rabbits: immunoelectron study. Br J Exp Path 1984; 65: 3553–64

    Google Scholar 

  113. Well-Knecht KJ, Zyzak DV, Litchfield JE, et al. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry 1995; 34: 3702–9

    Google Scholar 

  114. Vlassara H, Bucala R, Striker L. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest 1994; 70: 138–51

    PubMed  CAS  Google Scholar 

  115. Makita Z, Vlassara H, Cerani A, et al. Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem 1992; 267: 5133–8

    PubMed  CAS  Google Scholar 

  116. Schneider SL, Kohn RK. Effects of age and diabetes mellitus on the solubility of collagen from human skin, tracheal cartilage and dura mater. Exp Gerontol 1982; 17: 185–94

    Google Scholar 

  117. Kirstein M, Brett J, Radoff S, et al. Advanced protein glycosylation induces transendothelial human monocyte Chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. Proc Natl Acad Sci USA 1990; 87: 9010–4

    PubMed  CAS  Google Scholar 

  118. Vlassara H, Brownlee M, Cerani A. High affinity receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macro-molecules. Proc Natl Acad Sei USA 1985; 82: 5588–92

    CAS  Google Scholar 

  119. Vlassara H, Brownlee M, Cerani A. Novel macrophage receptor for glucose-modified protein is distinct from previously described scavenger receptors. J Exp Med 1986; 164: 1301–9

    PubMed  CAS  Google Scholar 

  120. Kirstein M, Aston C, Hintz R, et al. Receptor-specific induction of insulin-like growth factor I in human monocytes by advanced glycosylation end product-modified proteins. J Clin Invest 1992; 90, 439–46

    PubMed  CAS  Google Scholar 

  121. Ritthaler U, Deng Y, Zhang Y, et al. Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease. Am J Pathol 1995; 146, 688–94

    PubMed  CAS  Google Scholar 

  122. Bucala R, Tracey K, Cerani A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium dependent vasodilatation in experimental diabetes. J Clin Invest 1991; 87: 432–8

    PubMed  CAS  Google Scholar 

  123. Vlassara H, Fuh H, Makita Z, et al. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad SCI USA 1992; 89: 12043–7

    PubMed  CAS  Google Scholar 

  124. Bucala R, Makita Z, Koschinsky T, et al. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci USA 1993; 90: 6434–8

    PubMed  CAS  Google Scholar 

  125. Bucala R, Makita Z, Vega G, et al. Modification of low density lipoprotein by advanced glycation end products contributes to dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci USA 1994; 91, 9441–5

    PubMed  CAS  Google Scholar 

  126. Constantinides P. Cause of thrombosis in human atherosclerotic arteries. Am J Cardiol 1990; 66: 37G–40G

    PubMed  CAS  Google Scholar 

  127. Badimon JJ, Fuster V, Chesebro JH, et al. Coronary atherosclerosis. A multifactorial disease. Circulation 1993; 87 (II Suppl.): II3–16

    PubMed  CAS  Google Scholar 

  128. Shah PK, Forrester JS. Pathophysiology of acute coronary syndromes. Am J Cardiol 1991; 68: 16C–23C

    PubMed  CAS  Google Scholar 

  129. Ross R, Masuda J, Raines EW, et al. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science 1990; 248: 1009–12

    PubMed  CAS  Google Scholar 

  130. Galis ZS, Muszynsky M, Sukhova GK, et al. Enhanced expression of vascular matrix metalloproteinases induced in vitro by cytokines and in regions of human atherosclerotic lesions. Ann NY Acad Sci 1995; 17: 501–7

    Google Scholar 

  131. Li H, Freeman MW, Libby P. Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. J Clin Invest 1995; 95: 122–33

    PubMed  CAS  Google Scholar 

  132. Rosenfeld ME, Yla-Herttuala S, Lipton BA, et al. Macrophages colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. Am J Pathol 1992; 140: 291–300

    PubMed  CAS  Google Scholar 

  133. Wilcox JN, Smith KM, Willimas LT, et al. Platelet derived growth factor mRNA detection in human atherosclerosis by in situ hybridization. J Clin Invest 1988; 82: 1134–43

    PubMed  CAS  Google Scholar 

  134. Yla-Herttuala S, Lipton BA, Rosenfeld ME, et al. Macrophages express monocyte chemotactic protein in human and rabbit atherosclerotic lesions. Proc Natl Acad Sci USA 1991; 88: 5252–6

    PubMed  CAS  Google Scholar 

  135. Spagnoli LG, Mauriello A, Palmieri G, et al. Relationship between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis. Atherosclerosis 1994; 108: 39–60

    PubMed  CAS  Google Scholar 

  136. Spagnoli LG, Mauriello A, Palmieri G, et al. Heterogeneous morphological patterns of the fibroatheromatous plaque and risk factors. In: Wissler RW, editor. Atherosclerotic plaques. NATO ASI Series, Series A: life Sciences. Vol. 219. New York: Plenum Press, 1991: 27–37

    Google Scholar 

  137. Falk E. Why do plaques rupture? Circulation 1992; 86 (6 Suppl.): III30–42

    PubMed  CAS  Google Scholar 

  138. Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage and smooth muscle cell content. Br Heart J 1993; 69: 377–81

    PubMed  CAS  Google Scholar 

  139. Loree HM, Kamm RD, Stringfellow RG, et al. Effects of fibrous cap thickness on peak circumferential stress in model atherosclerotic vessels. Circ Res 1992; 71: 850–8

    PubMed  CAS  Google Scholar 

  140. Mayne R. Collagenous proteins of blood vessels. Arteriosclerosis 1986; 6: 585–93

    PubMed  CAS  Google Scholar 

  141. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983; 50: 127–34

    PubMed  CAS  Google Scholar 

  142. Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; 2: 941–4

    PubMed  CAS  Google Scholar 

  143. Matrisian LM. The matrix degrading metalloproteinases. Bioessays 1992; 14: 455–63

    PubMed  CAS  Google Scholar 

  144. Mitchinson MS, Ball RV. Macrophages and atherogenesis. Lancet 1982; 2: 146–7

    Google Scholar 

  145. Galis ZS, Sukhova GK, Kranzhofer R. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci USA 1995; 92: 402–6

    PubMed  CAS  Google Scholar 

  146. Nawroth PP, Stern DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740–5

    PubMed  CAS  Google Scholar 

  147. Watanabe N, Nitsu Y, Umeno H, et al. Toxic effect of tumor necrosis factor on tumor vasculature in mice. Cancer Res 1988; 48: 2179–83

    PubMed  CAS  Google Scholar 

  148. Arbustini E, Grasso M, Diegoli M, et al. Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical and biochemical study. Am J Cardiol 1991; 68: 36B–50B

    PubMed  CAS  Google Scholar 

  149. Barath P, Fishbein MC, Cao J, et al. Detection and localization of tumor necrosis factor in human atheroma. Am J Cardiol 1990; 65: 297–302

    PubMed  CAS  Google Scholar 

  150. Imparato AM, Riles TS, Gorstein F. The carotid bifurcation plaque: pathologic findings associated with cerebral ischemia. Stroke 1979; 10: 238–45

    PubMed  CAS  Google Scholar 

  151. Lushby RJ, Ferrell LD, Ehrenfeld WK, et al. Carotid plaque hemorrhage. Its role in production of cerebral ischemia. Arch Surg 1982; 117: 1479–88

    Google Scholar 

  152. Barger AC, Beeuwkes R. Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. Am J Cardiol 1990; 66: 41–3

    Google Scholar 

  153. Spagnoli LG, Bonanno E, Mauriello A, et al. Histopathological characterization of carotid plaques echotomography. Inter Angio 1988; 7: 75–80

    CAS  Google Scholar 

  154. Wartman WB. Vascularization and hemorrhage in arterial wall. In: Studies in pathology. Melbourne: University of Melbourne, 1950

    Google Scholar 

  155. Barger AC, Beeuwkes R, Lainey LL, et al. Hypothesis: vasa vasorum and neovascularization of human coronaries: a possible role in the pathology of atherosclerosis. N Engl J Med 1984; 310: 175–7

    PubMed  CAS  Google Scholar 

  156. Stary HC. The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur Heart J 1990; 11 (E Suppl.): 3–19

    PubMed  Google Scholar 

  157. Beadenkopf WG, Daoud AS, Love BM. Calcification in the coronary arteries and its relationship to arteriosclerosis and myocardial infarction. Am J Roentgenol 1964; 92: 865–71

    CAS  Google Scholar 

  158. Frink AJ, Achor RWP, Brown Jr AL, et al. Significance of calcification of the coronary arteries. Am J Cardiol 1970; 26: 241–7

    PubMed  CAS  Google Scholar 

  159. Agatson AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcification using ultrafast computed tomography. J Am Coll Cardiol 1990; 15: 827–32

    Google Scholar 

  160. Vlodaver Z, Neufeld H, Edwards JE. Pathology of coronary disease. Semin Roentgenol 1972; 7: 376–85

    PubMed  CAS  Google Scholar 

  161. Bostrom K, Watson KE, Horn C. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 1993; 91: 1800–9

    PubMed  CAS  Google Scholar 

  162. Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91: 2488–96

    PubMed  CAS  Google Scholar 

  163. Sangiorgi G, Srivatsa SS, Staab M, et al. Total coronary calcified volume is highly correlated with total plaque volume: a histologic study of 723 segments [abstract]. J Am Coll Cardiol 1995; (special issue): 386A

    Google Scholar 

  164. Fuster V, Badimon JJ, Badimon L. Clinical-pathological correlations of coronary disease progression and regression. Circulation 1992; 86 (6 Suppl.): 1–11

    Google Scholar 

  165. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet 1994; 344: 793–5

    PubMed  CAS  Google Scholar 

  166. Dzau VJ. Cell biology and genetics of angiotensin in cardiovascular disease. J Hypertens 1994; 12 Suppl.: S3–10

    CAS  Google Scholar 

  167. Holtz J, Goetz RM. Vascular renin-angiotensin-system, endothelial function and atherosclerosis? Basic Res Cardiol 1994; 89 (1 Suppl.): 71–86

    PubMed  CAS  Google Scholar 

  168. Constantinides P, Kiser M. Arterial effects of palmitic, linoleic and acetoacetic acid. Atherosclerosis 1981; 38: 309–19

    PubMed  CAS  Google Scholar 

  169. McGill HC. Smoking and the pathogenesis of atherosclerosis. In: Diana JN, editor. Tobacco smoking and atherosclerosis. Pathogenesis and cellular mechanism. Adv Exp Med Biol 1990; 273: 9–16

    Google Scholar 

  170. Zimmerman M, McGeachie J. The effect of nicotine on aortic endothelium. A quantitative ultrastructural study. Atherosclerosis 1987; 63: 33–41

    PubMed  CAS  Google Scholar 

  171. Pittilo RM. Cigarette smoking and endothelial injury: a review. In: Diana JN, editor. Tobacco smoking and atherosclerosis. Pathogenesis and cellular mechanism. Adv Exp Med Biol 1990; 273: 61–78

    CAS  Google Scholar 

  172. Lopez-Virella MF, Virella G. Atherosclerosis and autoimmunity. Clin Immunol Immunopathol 1994; 73: 155–67

    Google Scholar 

  173. Murphy EA, Roswell HE, Downie HG, et al. Encrustation and atherosclerosis: the analogy between early in vivo lesions and the deposits which occur in extra-corporeal circulations. Can Med Assoc J 1962; 87: 259–66

    PubMed  CAS  Google Scholar 

  174. Ludmer PL, Selwiyn AP, Shook TL, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046–51

    PubMed  CAS  Google Scholar 

  175. Chesebro JH, Zoldhelyi P, Fuster V. Plaque disruption and thrombosis in unstable angina pectoris. Am J Cardiol 1991; 68: 9C–15C

    PubMed  CAS  Google Scholar 

  176. Fuster V, Stein B, Ambrose JA, et al. Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation 1990; 82 (3 Suppl.): II47–59

    PubMed  CAS  Google Scholar 

  177. Roberts WC. Atherosclerosis risk factors: are there 10 or is there only 1? Am J Cardiol 1989; 64: 552–4

    PubMed  CAS  Google Scholar 

  178. Roberts WC. Factors linking cholesterol to atherosclerotic plaques. Am J Cardiol 1988; 62: 495–8

    PubMed  CAS  Google Scholar 

  179. Malmros H. The relation of nutrition to health: a statistical study of the effect of the war-time on atherosclerosis, cardiosclerosis, tuberculosis and diabetes. Acta Med Scand Suppl 1950; 246: 137–53

    PubMed  CAS  Google Scholar 

  180. Keys A. Nutrition in relation to the etiology and course of degenerative disease. J Am Diet Assoc 1948; 24: 281–5

    PubMed  CAS  Google Scholar 

  181. Wilens S. The resorption of arterial atheromatous deposits in wasting disease. Am J Pathol 1947; 23: 793–804

    PubMed  CAS  Google Scholar 

  182. Kuo PT, Hayase K, Kostis JB, et al. Use of combined diet and colestipol in long term (7–7½years) treatment of patients with type II hypercholesterolemia. Circulation 1979; 79: 199–214

    Google Scholar 

  183. Buchwald H, Moore RB, Varco RL. Surgical treatment of hypercholesterolemia. Circulation 1974; 49(I Suppl. I): I37–45

    Google Scholar 

  184. Stein EA, Adolph R, Rice V, et al. Non progression of coronary artery arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation 1984; 69: 313–24

    Google Scholar 

  185. Nikkila EA, Viikinkoski P, Valle M, et al. Prevention of progression of coronary atherosclerosis by treatment of hyperlipidemia: a seven year prospective angiographic study. BMJ 1984; 289: 220–3

    PubMed  CAS  Google Scholar 

  186. Arntzenius AC, Kromhout D, Barth JD, et al. Diet, lipoprotein and the progression of coronary atherosclerosis: the Leiden Intervention Trial. N Engl J Med 1985; 312: 805–11

    PubMed  CAS  Google Scholar 

  187. Blankenhorn DH, Nessim SA, Johnson RL, et al. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary atherosclerosis and coronary venous bypass grafts. JAMA 1987; 257: 3233–40

    PubMed  CAS  Google Scholar 

  188. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary artery disease? The Lifestyle Heart Trial. Lancet 1990; 332: 129–33

    Google Scholar 

  189. Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal bypass surgery on mortality from coronary artery disease in patients with hypercholesterolemia: report of the Program on the Surgical Control of the Hyperlipidemias (POSH). N Engl J Med 1990; 323: 946–55

    PubMed  CAS  Google Scholar 

  190. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323: 1289–98

    PubMed  CAS  Google Scholar 

  191. Kane JP, Malloy MJ, Ports TA, et al. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA 1990; 264: 3007–12

    PubMed  CAS  Google Scholar 

  192. Watts GF, Lewis B, Brunt JNH, et al. Effects on coronary artery disease of lipid lowering diet, or diet plus cholestyramine, in the St. Thomas Atherosclerosis Regression Study (STARS). Lancet 1992; 339: 563–99

    PubMed  CAS  Google Scholar 

  193. Alderman EL, Haskell WL, Fair JM, et al. Beneficial angiographic and clinical response to multifactor modification in the Stanford Coronary Risk Intervention Project (SCRIP) [abstract]. Circulation 1991; 84 (II Suppl.): II140

    Google Scholar 

  194. Schuler G, Hambrecht R, Schlierf G, et al. Myocardial perfusion and regression of coronary artery disease in patients on regimen of intensive physical exercise and low fat diet. J Am Coll Cardiol 1992; 19: 34–42

    PubMed  CAS  Google Scholar 

  195. Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovostatin therapy: the Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med 1993; 119: 969–76

    PubMed  CAS  Google Scholar 

  196. Waters D, Higginson L, Gladstone P, et al. Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography: the Canadian Coronary Atherosclerosis Intervention Trial. Circulation 1994; 89: 959–68

    PubMed  CAS  Google Scholar 

  197. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary artery disease: the Scandinavian Simvastatin Survival Study Group (4S). Lancet 1994; 344: 1383–9

    Google Scholar 

  198. Vogel RA. Hypolipidemic intervention and prospect for regression. In: Topol EJ, editor. Textbook of interventional cardiology. 2nd ed. Philadelphia: W.B. Saunders Co., 1994, 161–7

    Google Scholar 

  199. Rossouw JE. The effects of lowering serum cholesterol on coronary artery disease risk. Med Clin North Am 1994; 78: 181–95

    PubMed  CAS  Google Scholar 

  200. Sehayek E, Eisemberg S. Abnormal composition of hypertriglyceridemic very low density lipoprotein determines abnormal cell metabolism. Arteriosclerosis 1990; 10: 1088–96

    PubMed  CAS  Google Scholar 

  201. Tornvall P, Hamsten A, Johansson J, et al. Normalization of the composition of very low density lipoprotein in hypertriglyceridemia by nicotinic acid. Atherosclerosis 1990; 84; 219–27

    PubMed  CAS  Google Scholar 

  202. Sirtori CR, Lovati MR. Biguanides in hypertriglyceridemia and in management of arterial diseases. Atheroscler Rev 1991; 22: 155–62

    Google Scholar 

  203. Fritz IB. Carnitine and its role in fatty acid metabolism. Adv Lip Res 1963; 1: 285–98

    CAS  Google Scholar 

  204. Spagnoli LG, Orlandi A, Marino B, et al. Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits. Atherosclerosis 1995; 114: 29–44

    PubMed  CAS  Google Scholar 

  205. Di Lisia F, Menabò R, Siliprandi N. L-Propionyl-Carnitine protection of mitochondria in ischemic rat hearts. Mol Cell Biochem 1989; 88: 169–73

    Google Scholar 

  206. Liedke AJ, DeMaison L, Nellis SH. Effects of L-propionyl-carnitine on mechanical recovery during reflow in intact hearts. Am J Physiol 1988; 255: H169–76

    Google Scholar 

  207. Baker HN, Eggen DA, Melchior GV, et al. Lipoprotein profiles in rhesus monkeys with divergent responses to dietary cholesterol. Arteriosclerosis 1983; 3: 223–32

    PubMed  CAS  Google Scholar 

  208. Meade TW, Ruddock W, Stirling Y, et al. Fibrinolytic activity, clotting factors, and long term incidence of ischemic heart disease in the Northwick Park Heart Study. Lancet 1993; 324: 1076–9

    Google Scholar 

  209. Kelleher CC. Plasma fibrinogen and factor VII as a risk factors for cardiovascular disease. Eur J Epidemiol 1982: 8 (1 Suppl.): 79–82

    Google Scholar 

  210. De Michèle MA, Minnear FL. Modulation of vascular endothelial permeability by thrombin. Semin Thromb Hemos 1992; 18: 287–95

    Google Scholar 

  211. Bar-Shavit R, Benezra M, Eldor A, et al. Thrombin immobilized to extracellular matrix is a potent mitogen for vascular smooth muscle cells: nonenzymatic mode of action. Cell Regul 1990; 1: 453–63

    PubMed  CAS  Google Scholar 

  212. Smith EB, Crosbie L. Does lipoprotein Lp(a) compete with plasminogen in human atherosclerotic lesions and thrombi? Atherosclerosis 1991; 89: 127–36

    PubMed  CAS  Google Scholar 

  213. Dahlen GH, Guyton GR, Attar M, et al. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography. Circulation 1986; 4: 758–65

    Google Scholar 

  214. Abe A, Noma A, Lee YJ, et al. Studies on apoliprotein (a) phenotypes: 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery disease. Atherosclerosis 1992; 96: 9–15

    PubMed  CAS  Google Scholar 

  215. Kramsch DM, Blankenborn DH. Response to aggressive lipid lowering in angiographic trials (CLAS, MARS) is driven by lesion composition. Cardiovasc Drug Ther 1993; 7 (2 Suppl.): 397

    Google Scholar 

  216. Kannel WB, Gordon T. Evaluation of cardiovascular risk in the elderly: the Framingham Study. Bull NY Acad Med 1978; 54: 573–91

    CAS  Google Scholar 

  217. Larochelle P. Hypertension in the elderly. Cardiovasc Drugs Ther 1990; 4 (5 Suppl.): 947–50

    PubMed  Google Scholar 

  218. Lindholm LH, Ekbom T. Hypertension in the elderly. Clin Exp Hypertens 1993; 15: 1343–52

    PubMed  CAS  Google Scholar 

  219. Joint National Committee. The 1988 Report of the Joint National Committee on detection, evaluation and treatment of high blood pressure. Arch Intern Med 1988; 148: 1023–38

    Google Scholar 

  220. Davidson RA. Hypertension in the elderly. Med Clin North Am 1989; 73: 1471–81

    PubMed  CAS  Google Scholar 

  221. Staessen J, Fagard R, Amery A. Isolated systolic hypertension in the elderly: implications of Systolic Hypertension in the Elderly Program (SHEP) for clinical practice and for the ongoing trials. J Hum Hypertens 1991; 5: 469–74

    PubMed  CAS  Google Scholar 

  222. Bulpitt CJ, Fletcher AE. Aging, blood pressure and mortality. J Hypertens 1992; 10 Suppl.: S45–9

    Google Scholar 

  223. Julius S. The therapeutic dilemma of hypertension in the elderly. Drugs 1988; 36: 7–17

    PubMed  Google Scholar 

  224. Burris JF. Practical considerations in treating the elderly hypertensive patient. Am J Med 1991; 90: 28S–31S

    PubMed  CAS  Google Scholar 

  225. Hansson L. Future goals for the treatment of hypertension in the elderly with reference to STOP-Hypertension, SHEP and the MRC trial in older adults. Am J Hypertens 1993; 6: 40S–3S

    PubMed  CAS  Google Scholar 

  226. MacMahon S, Rodgers A. The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Clin Exp Hypertens 1993; 15: 967–78

    PubMed  CAS  Google Scholar 

  227. Shapiro DA, Liss CL, Walker JF, et al. Enalapril and hydrochlorothiazide as antihypertensive agents in the elderly. J Cardiovasc Pharmacol 1987; 10: S160–2

    PubMed  Google Scholar 

  228. Massie BM. Demographic considerations in the selection of antihypertensive therapy. Am J Cardiol 1987; 60: 121L–6L

    Google Scholar 

  229. Cressman MD, Gifford RW, Vidt DG. Geriatric hypertension controversies. Uses of new agents. Geriatrics 1985; 40: 53–68

    PubMed  CAS  Google Scholar 

  230. Clark BK. Beta-adrenergic blocking agents: their current status. AACN Clin Issues Crit Care Nurs 1992; 3: 447–60

    PubMed  CAS  Google Scholar 

  231. Grimm RH, Leon AS, Hunninghake GW. Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive men. Ann Intern Med 1981; 94: 7–11

    PubMed  Google Scholar 

  232. Cruickshank JM. B-blockers, plasma lipids and coronary heart disease. Circulation 1990; 82 (II Suppl.): 1160–5

    Google Scholar 

  233. Busse JC, Materson BJ. Geriatric hypertension. The growing use of calcium-channel blockers. Geriatrics 1988; 43: 51–8

    PubMed  CAS  Google Scholar 

  234. Ng LL, Davies JE, Wojcikiewicz RJH. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibition modulates vasopressin-stimulated Ca2+responses in rat A10 vascular smooth muscle cells. Circ Res 1994; 74: 173–81

    PubMed  CAS  Google Scholar 

  235. Parmely WW. Calcium-channel blockers in the prevention of atherosclerosis. In: Masserli FH, editor. Cardiovascular drug therapy. Philadelphia: Saunders, 1990

    Google Scholar 

  236. Weinstein DB, Heider JC. Antiatherogenic properties of calcium antagonist. Am J Cardiol 1987; 59: 163b

    PubMed  CAS  Google Scholar 

  237. Loaldi A, Polese A, Montorsi P, et al. Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina factors. Am J Cardiol 1989; 64: 433–40

    PubMed  CAS  Google Scholar 

  238. Storz G, Tartaglia LA, Ames BN. Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation. Science 1990; 248: 189–94

    PubMed  CAS  Google Scholar 

  239. Marui N, Offermann MK, Swerlich R, et al. Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cell. J Clin Invest 1993; 92: 1866–74

    PubMed  CAS  Google Scholar 

  240. Jackson RL. Anti-oxidants for the treatment and prevention of atherosclerosis. Biochem Soc Trans 1993; 21(Pt 3): 650–1

    PubMed  CAS  Google Scholar 

  241. Heinecke J, Baker L, Rosen H, et al. Superoxide-mediated modifications of low density lipoprotein by arterial smooth muscle cells. J Clin Invest 1986; 77: 641–4

    Google Scholar 

  242. Carew T, Schwenke D, Steinberg D. Antiatherogenic effect of probucol unrelated to its hypercholesterolemic effect: evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage-rich fatty streaks and slow progression of atherosclerosis in the Watanabe heritable hyperlipidemic rabbit. Proc Natl Acad Sci 1987; 84: 7725–9

    PubMed  CAS  Google Scholar 

  243. Gey KF, Puska P, Jordan P, et al. Inverse correlation between plasma vitamin E and mortality from ischemic heart disease in cross-cultural epidemiology. Am J Nutr 1991; 53 (1 Suppl): 326S–334S

    CAS  Google Scholar 

  244. Riemersma RA, Wood DA, Macintyre CCA, et al. Risk of angina pectoris and plasma concentration of vitamin A, C and E and carotene. Lancet 1991; 1: 1–5

    Google Scholar 

  245. Steinber D. Antioxidants in the prevention of human atherosclerosis. Summary of the proceedings of a National Hearts, Lung and Blood Institute workshop: 1991 Sep 5–6; Bethesda, Maryland. Circulation 1992; 85: 2337–44

    Google Scholar 

  246. Weiner BH, Ockene IS, Levine PH, et al. Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model. N Engl J Med 1986; 315: 841–6

    PubMed  CAS  Google Scholar 

  247. Davis HR, Bridenstine RT, Vesselinovitch D, et al. Fish oil inhibits the development of atherosclerosis in rhesus monkeys. Atherosclerosis 1987; 7: 441–9

    CAS  Google Scholar 

  248. Llera-Moya M, Rothblat GH, Glick JM, et al. Etoposide treatment suppresses atherosclerotic plaque development in cholesterol-fed rabbits. Arterioscler Thromb 1992; 12: 1363–70

    PubMed  Google Scholar 

  249. Cavallero C, Turolla E, Ricevuti G. Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits. Atherosclerosis 1971; 13: 9–20

    PubMed  CAS  Google Scholar 

  250. Cavallero C, Di Tondo U, Mingazzini L, et al. Cell proliferation in the atherosclerotic lesions of cholesterol-fed rabbits. Part II: histological, ultrastructural and radioautographic observations on epinephrine-treated rabbits. Atherosclerosis 1973; 17: 49–62

    PubMed  CAS  Google Scholar 

  251. Cavallero C, De Lellis C, Di Tondo U, et al. Reactive and proliferative changes of the arterial smooth muscle in experimental atherosclerosis: hormonal control. In: Cavallero C, editor. The arterial wall in atherogenesis. Padova: Piccin Medical Books, 1975: 25–42

    Google Scholar 

  252. Cavallero C, Di Tondo U, Mingazzini P, et al. Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits. Part III: histological and radioautographic observations on glucocorticoid treated rabbits. Atherosclerosis 1976; 25: 145–52

    PubMed  CAS  Google Scholar 

  253. Spagnoli LG, Palmieri G, Mauriello A, et al. High-dose synthetic progestogens inhibit foam and smooth muscle cell proliferation and atherosclerotic plaques formation in aortas of rabbits fed a hypercholesterolemic diet. Atherosclerosis 1990; 82: 27–36

    PubMed  CAS  Google Scholar 

  254. Asai K, Funaki C, Hayashi T, et al. Dexamethasone-induced suppression of aortic atherosclerosis in cholesterol fed rabbits. Arterioscl Thromb 1993; 13: 892–9

    PubMed  CAS  Google Scholar 

  255. Stein O, Halperin G, Stein Y. Long-term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolemic serum. Arteriosclerosis 1987; 7: 585–92

    PubMed  CAS  Google Scholar 

  256. Cheung WT, Shi MM, Young JD, et al. Inhibition of radioligand binding to A1 adenosine receptors by Bay K 8644 and nifedipine. Biochem Pharmacol 1987; 36: 2183–9

    PubMed  CAS  Google Scholar 

  257. Corsini A, Raiteri M, Soma M, et al. Simvastatin but not pravastatin inhibits the proliferation of rat myocytes. Pharmacol Res 1991; 23: 173–80

    PubMed  CAS  Google Scholar 

  258. Muller DWM, Topol EJ, Abrams J, et al. Intramural methotrexate therapy for the prevention of neointimal thickening after balloon angioplasty. J Am Coll Cardiol 1992; 20: 460–6

    PubMed  CAS  Google Scholar 

  259. Gimple LW, Gertz SD, Haber HL, et al. Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits: a quantitative angiographic and histopathological study. Circulation 1992; 86: 1536–46

    PubMed  CAS  Google Scholar 

  260. Wilensky RL, Gradus-Pizlo I, March KL, et al. Efficacy of local intramural injection of colchicine in reducing restenosis following angioplasty in the atherosclerotic rabbit model [abstract]. Circulation 1992; 86: 1–52

    Google Scholar 

  261. Chester AH, O’Neil GS, Tadjkarimi S, et al. The role of nitric oxide in mediating endothelium dependent relaxations in human epicardial coronary artery. Int J Cardiol 1990; 29: 305–9

    PubMed  CAS  Google Scholar 

  262. Gotto Jr AM. Dyslipidemia and atherosclerosis. A forecast of pharmaceutical approaches. Circulation 1993; 87 (III Suppl.): III54–9

    PubMed  Google Scholar 

  263. Wilson JM, Grossmann M, Raper SE, et al. Ex vivo gene therapy of familial hypercholesterolemia. Hum Gene Ther 1992; 3: 179–222

    PubMed  CAS  Google Scholar 

  264. Huby R, Harding JJ. Non-enzymatic glycosylation (glycation) of lens proteins by galactose and protection by aspirin and reduced glutathione. Exp Eye Res 1988; 47: 53–9

    PubMed  CAS  Google Scholar 

  265. Solomon LR, Cohen K. Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes 1989; 38: 881–6

    PubMed  CAS  Google Scholar 

  266. McPherson JD, Shilton BH, Walton DJ. Role of fructose in glycation and cross-linking of proteins. Biochemistry 1988; 27: 1901–7

    PubMed  CAS  Google Scholar 

  267. Brownlee M, Vlassara H, Kooney T, et al. Aminoguanidine prevents diabetes-induced arterial wall protein crosslinking. Science 1986; 232: 1629–32

    PubMed  CAS  Google Scholar 

  268. Nicholls K, Mandel TE. Advanced glycosylation end products in experimental murine diabetic nephropathy: effect of islet isografting and of aminoguanidine. Lab Invest 1989; 60: 486–93

    PubMed  CAS  Google Scholar 

  269. Brownlee M. Glycosylation products as toxic-mediators of diabetic complications. Annu Rev Med 1991; 42: 159–66

    PubMed  CAS  Google Scholar 

  270. Kinhara M, Schmelzer JD, Poduslo JF, et al. Aminoguanidine effects on nerve blood flow, vascular permeability, electro-physiology, and oxygen free radicals. Proc Natl Acad Sci USA 1991; 88: 6107–11

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cattedra di Anatomia ed Istologia Patologica, University of Rome ‘Tor Vergata’, Rome, Italy

    Luigi Giusto Spagnoli, Alessandro Mauriello, Augusto Orlandi, Giuseppe Sangiorgi & Elena Bonanno

Authors
  1. Luigi Giusto Spagnoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandro Mauriello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Augusto Orlandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Sangiorgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elena Bonanno
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spagnoli, L.G., Mauriello, A., Orlandi, A. et al. Age-Related Changes Affecting Atherosclerotic Risk. Drugs & Aging 8, 275–298 (1996). https://doi.org/10.2165/00002512-199608040-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199608040-00004

Keywords

Search

Navigation