Skip to main content

Advertisement

SpringerLink
Log in

Arterial wall cholesterol content is a predictor of development and severity of arterial thrombosis

  • Featured Translational Investigation
  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Background: It is unclear if total cholesterol content contributes to the severity of cardiovascular events by affecting the amount of thrombosis. This study evaluated relationships between cholesterol levels and the amount of thrombosis in an atherosclerotic rabbit model of plaque disruption and thrombosis.

Methods: Three groups of NZW rabbits were used: normal rabbits (Group I, n = 4); atherosclerotic rabbits (Group II, n = 4); and atherosclerotic rabbits with pharmacologically triggered thrombosis (Group III, n = 16). Atherosclerosis was induced by feeding a cholesterol enriched diet and balloon deendothelialization. At post-mortem, platelet-rich thrombus and arterial wall cholesterol were quantified and histology performed by light and electron microscopy.

Results: Arterial wall cholesterol was strongly correlated to serum cholesterol in all groups (r = 0.94, p < 0.0001). There was a significant correlation between the thrombus surface area with arterial wall cholesterol in Group III (r = 0.71, p < 0.002). Serum cholesterol, arterial wall cholesterol, and thrombus surface area were all significantly correlated but only arterial wall cholesterol was an independent predictor of thrombosis. A threshold specific for this model was noted for serum and arterial cholesterol levels above which thrombosis consistently occurred.

Conclusions: Arterial wall cholesterol was strongly correlated to serum cholesterol and thrombosis severity. Serum cholesterol, arterial wall cholesterol and thrombus surface area were all integrally related.

Condensed Abstract

A model of plaque disruption and thrombosis was used to demonstrate a correlation between serum and arterial wall cholesterol (r = 0.94; p < 0.0001); arterial wall cholesterol and the amount of thrombosis (surface area; r = 0.71, p < 0.002). A threshold of serum and arterial cholesterol was determined at which thrombosis occurred in this model.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Abela GS, Picon PD, Friedl SE, et al (1995) Triggering of plaque disruption and arterial thrombosis in an atherosclerotic rabbit model. Circulation 91:776–784

    PubMed  CAS  Google Scholar 

  2. Constantinides P, Chakravarti RN (1961) Rabbit arterial thrombosis production by systemic procedures. Arch Pathol 72:197–208

    PubMed  CAS  Google Scholar 

  3. Christov A, Dai E, Drangova M, et al (2000) Optical detection of triggered atherosclerotic plaque disruption by fluorescence emission analysis. J Photochem Photobiol 72:242–252

    Article  CAS  Google Scholar 

  4. Johnstone MT, Botnar RM, Perez AS, et al (2000) In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model. Thromb Vasc Biol 21:1556–1560

    Google Scholar 

  5. Davies MJ, Thomas AC (1985) Plaque fissuring: The cause of acute myocardial infarction causing sudden ischaemic death, and crecendo angina. Br Heart J 53:363–373

    PubMed  CAS  Google Scholar 

  6. Muller JE, Abela GS, Nesto RW, Tofler GH (1994) Triggers, acute risk factors, and vulnerable plaques: The lexicon of a new frontier. J Am Coll Cardiol 23:809–813

    PubMed  CAS  Google Scholar 

  7. Libby P (1995) Molecular bases of the acute coronary syndrome. Circulation 91:2844–2850

    PubMed  CAS  Google Scholar 

  8. Lendon CL, Davies MJ, Born GVR, Richardson PD (1991) Atherosclerotic plaque caps are locally weakened when macrophages density is increased. Atherosclerosis 87:87–90

    Article  PubMed  CAS  Google Scholar 

  9. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J (1993) Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, marcrophage, and smooth muscle cell content. Br Heart J 69:377–381

    PubMed  CAS  Google Scholar 

  10. Li H, Cybulsky MI, Gimbrone MA, Libby P (1993) An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb 13:197–204

    PubMed  Google Scholar 

  11. Aikawa M, Voglic SJ, Sugiyama S, et al (1999) Dietary lipid lowering reduces tissue factor expression in rabbit atheroma. Circulation 100:1215–1222

    PubMed  CAS  Google Scholar 

  12. Loree HM, Kamm RD, Stringfellow RG, Lee RT (1992) Effects of fibrous cap thickness on peak circumferential stess in model atheroscelrotic vessels. Circ Res 71:850–858

    PubMed  CAS  Google Scholar 

  13. Castelli WP, Anderson K, Wilson PW, Levy D (1992) Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol 2:23–28

    Article  PubMed  CAS  Google Scholar 

  14. The Multiple risk factor intervention trial (MRFIT) (1976) A national study of primary prevention of coronary heart disease. JAMA 235:825–827

    Google Scholar 

  15. Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O’Neill WW (2000) Multiple complex coronary plaques in patients with acute myocardial infarction. N Eng J Med 343:915–922

    Article  CAS  Google Scholar 

  16. Qiao JH, Fisbein MC (1991) The severity of coronary atherosclerosis at sites of plaque rupture with occlusive thrombosis. J Am Coll Card 17:1138–1142

    Article  CAS  Google Scholar 

  17. Thompson PD, Moyna NM, White CM, Weber KM, Giri S, Waters DD (2002) The effects of hydroxy-methyl-glutaryl co-enzyme A reductase inbhibitors on platelet thrombus formation. Atherosclerosis 16:301–306

    Article  Google Scholar 

  18. Dangas G, Badimon JJ, Smith DA, et al (1999) Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. J Am Coll Cardiol 33:1294–1304

    Article  PubMed  CAS  Google Scholar 

  19. Kim JC, Chung TH (1984) Direct determination of free cholesterol and individual cholesterol esters in serum by high pressure liquid chromatography. Korean J Biochem 16:69–77

    CAS  Google Scholar 

  20. Little WC, Constanitinescu M, Applegate RJ, et al (1988) Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mid-to-moderate coronary artery disease? Circulation 78:1157–1166

    Google Scholar 

  21. Ueda Y, Asakura M, Hirayama A, Komamura K, Hori M, Kodama K (1996) Intracoronary morphology of culprit lesions after reperfusion in acute myocardial infarction: Serial angioscopic observations. J Am Coll Cardiol 27:606–610

    Google Scholar 

  22. Salonen JT, Salonen R (1991) Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 11:1245–1249

    PubMed  CAS  Google Scholar 

  23. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE (1993) Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. N Engl J Med 329:1677–1683

    Article  PubMed  CAS  Google Scholar 

  24. Tofler GH, Stone PH, Maclure M, et al (1990) Analysis of possible triggers of acute myocardial infarction. Am J Cardiol 66:22–27

    Article  PubMed  CAS  Google Scholar 

  25. Tofler GH, Brezinski D, Schafer AI, et al (1987) Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Eng J Med 316:1514–1518

    Article  CAS  Google Scholar 

  26. Sagel J, Colwell JA, Crook L, Laimins M (1975) Increased platelet aggregation in early diabetes mellitus. Ann Int Med 82:733–738

    PubMed  CAS  Google Scholar 

  27. Shepherd J, Cobbe SM, Ford I, et al (1995) for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Eng J Med 333:1301–1307

    Article  CAS  Google Scholar 

  28. The Scandinavian Survival Study Group (1994) Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Survival Study (4S). Lancet 344:1383–1389

    Google Scholar 

  29. Staprans I, Pan XM, Rapp JH, Feingold KR (1998) Oxidized cholesterol in the diet accelerates the development of aortic atherosclerosis in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol 18:977–983

    PubMed  CAS  Google Scholar 

  30. Ridker PM, Cannon CP, Morrow D, et al (2005) C-Reactive protein levels and outcomes after statin therapy. N Engl J Med 352:20–28

    Article  PubMed  CAS  Google Scholar 

  31. Nissen SE, Tuzcu EM, Schoenhagen, et al (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352:29–38

  32. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D (1997) Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 96:2097–2099

    Google Scholar 

  33. Toschi V, Gallo R, Lettino M, et al (1997) Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 95:594–599

    PubMed  CAS  Google Scholar 

  34. Maier W, Altwegg LA, Corti R, et al (2005) Inflammatory markers at the site of ruptured plaque in acute myocardial infarction. Circulation 111:1355–1361

    Article  PubMed  CAS  Google Scholar 

  35. Virk IS, Claycombe K, Ma H, et al (2004) Rising Levels of CRP and PAI-1 After Plaque Disruption Are Associated with Thrombosis. Circulation (abstr) 110:1486

    Google Scholar 

  36. Danenberg HD, Szalai AJ, Swaminathan RV, et al (2003) Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 108:512–515

    Article  PubMed  CAS  Google Scholar 

  37. Burke GL, Evans GW, Riley WA, et al (1995) Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke 26:386–391

    PubMed  CAS  Google Scholar 

  38. Abela GS, Aziz K (2005) Cholesterol crystals cause mechanical damage to biological membranes: A proposed mechanism of plaque rupture and erosion leading to arterial thrombosis. Clin Card 28:413–420

    Google Scholar 

  39. Abela GS, Aziz K (2006) Cholesterol crystals rupture biological membranes and human plaques during acute cardiovascular events: a novel insight into plaque rupture by scanning electron microscopy. Scanning 28:1–10

    Article  PubMed  CAS  Google Scholar 

  40. Abela GS, Eisenberg JD, Mittleman M, et al (1999) Detecting and differentiating white from red coronary thrombus by angiography in angina pectoris and in acute myocardial infarction. Am J Card 83:94–97

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Cardiology, Michigan State University, East Lansing, Michigan, 48824, USA

    Hongbao Ma, Kusai S. Aziz, Ruiping Huang & George S. Abela

Authors
  1. Hongbao Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kusai S. Aziz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruiping Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George S. Abela
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George S. Abela.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, H., Aziz, K.S., Huang, R. et al. Arterial wall cholesterol content is a predictor of development and severity of arterial thrombosis. J Thromb Thrombolysis 22, 5–11 (2006). https://doi.org/10.1007/s11239-006-7861-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-006-7861-x

Keywords

Search

Navigation