Diastolic Dysfuncion, Redox Stress, Extracellular Matrix Remodeling and Congestive Heart Failure in Diabetes Mellitus

  • M. R. Hayden
  • Suresh C. Tyagi
Part of the Progress in Experimental Cardiology book series (PREC, volume 9)


Congestive heart failure (CHF) is the one cardiovascular disease that has been increasing exponentially during the past decade. The current epidemic can only be expected to increase in the near future as our societies age. Hypertension (HTN), coronary artery disease (CAD), diabetes, and aging are currently the four big players and contribute to redox stress, myocellular and extramyocellular matrix (ECM) remodeling on the path to developing diastolic dysfunction (DD), systolic dysfunction (SD) and eventual CHF. The natural progression and history of CHF has a tendency to follow along two separate but interconnecting pathways as if tied together in a molecule. The roles of each of these factors will be discussed and the transition from DD to SD and overt CHF will be explored. Earlier diagnosis and compliance to current treatment paradigms by both the patient and physician are essential elements to slow or halt this progressive epidemic. Understanding the natural history of this morbid progressive disease will allow researchers and clinicians alike to develop novel treatment strategies and pave the way for newer developments in the diagnosis and treatment of CHF.

Key words

Congestive heart failure diastolic dysfunction systolic dysfunction redox stress and extracellular matrix remodeling 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Vasan RS, Levy D. 1996. The role of hypertension in the pathogenesis of heart failure: A clinical mechanistic overview. Arch Intern Med 156:1789–1796.PubMedCrossRefGoogle Scholar
  2. 2.
    Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK. 1996. The progression from hypertension to congestive heart failure. JAMA. May 275(20): 1604–1606.CrossRefGoogle Scholar
  3. 3.
    Remme WJ. 2000. Overview of the relationship between ischemia and congestive heart failure. Clin Cardiol. 23(7)(Suppl.IV):IV-4–IV-8.Google Scholar
  4. 4.
    American Heart Association. 1998. 1999 Heart and Stroke Statistical Update. American Heart Association. Dallas, Texas.Google Scholar
  5. 5.
    Gomberg-Maitland M, Baran DA, Fuster V 2001. Treatment of Congestive Heart Failure Guidelines for the primary care physician and the heart failure specialist. Arch Intern Med. Feb 161:342–352.PubMedCrossRefGoogle Scholar
  6. 6.
    Bonneux L, Barendregt JJ, Meeter K, Bonsel GJ, van der Maas PJ. 1994. Estimating clinical morbidity due to ischemic heart disease and congestive heart failure: The future rise of heart failure. Am J Public Health. 84:20–28.PubMedCrossRefGoogle Scholar
  7. 7.
    Glasser SP. 2001. Hypertension syndrome and cardiovascular events: High blood pressure is only one risk factor. Postgraduate Medicine November 110(5):29–36.Google Scholar
  8. 8.
    Vasan RS, Larson MG, Benjamin EF, Evans JC, Reiss C, Levy D. 1999. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in population-based cohort. J Am Coll Cardiol. 33:1948–1955.PubMedCrossRefGoogle Scholar
  9. 9.
    Mosterd A, Hoes AW, deBruyne MC, Deckers JW, Linker DT, Hofman A, Grobbee DE. 1999. Prevalence of heart failure and left ventricular dysfunction in the general population: the Rotterdam Study. Eur Heart J 20:447–455.PubMedCrossRefGoogle Scholar
  10. 10.
    Kupari M, Lindroos M, Iivanainen AM, Heikkila J, Tilvis R. 1997. Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis in the Helsinki Ageing Study. J Intern Med 241: 387–394.PubMedCrossRefGoogle Scholar
  11. 11.
    Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, Redfield MM. 1998. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 98:2282–2289.PubMedCrossRefGoogle Scholar
  12. 12.
    Vasan RS, Levy D. 2000. Defining diastolic heart failure: A call for standardized diagnostic criteria. Circulation. 101 (17):2118–2126.PubMedCrossRefGoogle Scholar
  13. 13.
    Weber KT. 1997. Extracellular matrix remodeling in heart failure: A role for de novo angiotensin II generation. Circulation. 96:4065–4082.PubMedCrossRefGoogle Scholar
  14. 14.
    Chatham JC, Forder JR, McNeill JH. 1996. The Heart in Diabetes. Kluwer Academic Publishers, Boston.CrossRefGoogle Scholar
  15. 15.
    Kannel WB, Hjortland, Castelli WP. 1974. Role of diabetes in congestive heart failure: The Framingham Study. Am J Cardiol 34:29.PubMedCrossRefGoogle Scholar
  16. 16.
    Sowers JR, Epstein M. 1995. Diabetes mellitus and associated hypertension, vascular disease, and Nephropathy. Hypertension 26:869–879.PubMedCrossRefGoogle Scholar
  17. 17.
    Sowers JR, Epstein M, Frohlich ED. 2001. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension Apr 37(4):1053–1059.CrossRefGoogle Scholar
  18. 18.
    Zabalgoitia M, Ismaeil MF, Anderson L, Maklady FA. 2001. Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus. Am J Cardiol Feb 1;87(3):320–323CrossRefGoogle Scholar
  19. 19.
    Griendling KK, Sorescu D. Masuko U-F. 2000. NAD(P)H Oxidase Role in cardiovascular biology and disease. Circulation Research 86(5):494.PubMedCrossRefGoogle Scholar
  20. 20.
    Babior BM. 1999. NADPH oxidase: an update. Blood 93(5): 1464–1476.PubMedGoogle Scholar
  21. 21.
    McCord JM, Fridovich I. 1988. Superoxide dismutase: the first twenty years (1968–1988). Free Radie Biol Med 5(5–6):363–369.CrossRefGoogle Scholar
  22. 22.
    Roos D, Weening RS, Wyss SR, Aebi HE. 1980. Protection of human neutrophils by endogenous catalase: Studies with cells from catalase-deficient individuals. J Clin Invest 65(6): 1515–1522.PubMedCrossRefGoogle Scholar
  23. 23.
    Lawrence RA, Burk RF. 1978. Species, tissue and subcellular distribution of selenium dependent, glutathione peroxidase activity. J Nutr 108(6):981–987.PubMedGoogle Scholar
  24. 24.
    Tyagi SC, Ratajska A, Weber KT. 1993. Myocardial matrix metalloproteinases: Localization and activation. Mol Cell Biochem. 126:49–59.PubMedCrossRefGoogle Scholar
  25. 25.
    25. Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. 1996. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. J Clin Invest 98:2572–2579.PubMedCrossRefGoogle Scholar
  26. 26.
    Lefer DJ, Granger DN. 2000. Oxidative stress and cardiac disease. Am J Med Sep 109(4):315–323.CrossRefGoogle Scholar
  27. 27.
    Dhalla NS, Elmoselhi AB, Hata T, Makino N. 2000. Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res Aug 18;47(3):446–456.CrossRefGoogle Scholar
  28. 28.
    Sigusch HH, Campbell SE, Weber KT. 1996. Angiotensin II-induced myocardial fibrosis in rats: Role of nitric oxide, prostaglandins and bradykinin. Cardiovasc Res 31:546–554.PubMedGoogle Scholar
  29. 29.
    Booz GW, Baker KM. 1995. Molecular signaling mechanisms controlling growth and function of cardiac fibroblasts. Cardiovasc Res 30:537–543.PubMedGoogle Scholar
  30. 30.
    Kolpakov V, Gordon D, Kulik TJ. 1995. Nitric oxide-generating compounds inhibit total protein and collagen synthesis in cultured vascular smooth muscle cell. Circ Res 76:305–309.PubMedCrossRefGoogle Scholar
  31. 31.
    Hingtgen SD, Davisson RL. 2001. Gene therapeutic approaches to oxidative stress-induced cardiac disease: principles, progress, and prospects. Antiox Redox Signal Jun 3(3):433–449CrossRefGoogle Scholar
  32. 32.
    Tyagi SC. 1999. Homocyst(e)ine and heart disease: Pathophysiology of extracellular matrix. Clin and Exper Hypertension 21 (3): 181–198.CrossRefGoogle Scholar
  33. 33.
    Mujumdar VS, Hayden MR, Tyagi SC. 2000. Homocyst(e)ine induces calcium second messenger in vascular smooth muscle cells. Journal of Cellular Physiology 183:28–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Meredith JE Jr., Fazeli B, Schwartz MA. 1993. The extracellular matrix as a cell survival factor. Mol Biol Cell 4(9):953–961.PubMedGoogle Scholar
  35. 35.
    Rossi MA, Abreu MA, Santoro LB. 1998. Connective tissue skeleton of the human heart. A demonstration by cell-maceration scanning electron microscope method. Circulation 97:934–935.PubMedCrossRefGoogle Scholar
  36. 36.
    Weber KT, Janicki JS, Pick R. Disruption of collagen tethers: Anatomic basis of muscle fiber slippage in the myocardium. Pages 18–35.Google Scholar
  37. 37.
    Jacob Seipel Zucker: Cardiac Dilatation. Gustav Fischer Verlag. Stuttgart. New York. 1990.Google Scholar
  38. 38.
    Weber KT. 1997. Extracellular matrix remodeling in heart failure: A role for De Novo angiotensin II generation. Circulation 96:4065–4082.PubMedCrossRefGoogle Scholar
  39. 39.
    Francis GS. 1998. Changing the remodeling process in heart failure: basic mechanisms and laboratory results. Curr Opin Cardiol 13(3): 156–161.PubMedGoogle Scholar
  40. 40.
    Weber KT. 2001. Aldosterone in congestive heart failure. Dec 345:1689–1697.Google Scholar
  41. 41.
    Heart Protection Study Collaborative Group. 2002. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360(9326):7–22.CrossRefGoogle Scholar
  42. 42.
    Zannad F, Alla F, Dousset B, Perez A, Pitt B, RALES Investigators. 2000. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the Randomized Aldactone Evaluation Study (RALES). Circulation 2000; 102: 2700–2706. [Erratum, Circulation 2001; 103:476.PubMedCrossRefGoogle Scholar
  43. 43.
    Cohn JN, Bristow MR, Chien KR, Colucci WS, Frazier OH, Leinwand LA, Lorell BH, Moss AJ, Sonnenblick EH, Walsh RA, Mockrin SC, Reinlib L. 1997. Report of the National Heart, Lung, and Blood Institute Special Emphasis Panel on Heart failure Research. Circulation. 95:766–770.PubMedCrossRefGoogle Scholar
  44. 44.
    Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P. 2002. Chimerism of the transplanted Heart. NEJM January 3 346(1):5–15.CrossRefGoogle Scholar
  45. 45.
    Li H, Simon H, Bocan TM, Peterson JT 2000. MMP/TIMP expression in spontaneously hypertensive heart failure rats: The effect of ACE-and MMP-inhibition. Cardiovasc Res 46(2):298–306.PubMedCrossRefGoogle Scholar
  46. 46.
    Naglich JG, Jure-Kunkel M, Gupta E, Fargnoli J, Henderson AJ, Lewin AC, Talbott R, Baxter A, Bird J, Savopoulos R, Wills R, Kramer RA, Trail PA. 2001. Inhibition of angiogenesis and Metastasis in two murine models by the matrix metalloproteinases inhibitor, BMS-275291. Cancer Res 61(23):8480–8485.PubMedGoogle Scholar
  47. 47.
    Vesely DL. 1999. Atrial natriuretic peptides in the diagnosis and treatment of congestive heart failure. Congestive Heart Failure 5:171–179.PubMedGoogle Scholar
  48. 48.
    Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B,Turi ZG, Hess OM. 2001. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. Nov 345(22): 1593–1600.Google Scholar
  49. 49.
    Homocysteine: The new risk factor: Introduction of patient management. March 1999; Professional Postgraduate Services ® (PPS), a division of Physicians World Communications Group, 400 Plaza Drive, Secaucus, NJ 07094.Google Scholar
  50. 50.
    Banas J. 1999. New insights into effects of statins on the atherosclerotic process. Cardiology Review Dec 16(12) (Suppl):1–4.Google Scholar
  51. Takemoto M, Liao JK. 2001. Pleiotropic Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arteriosclerosis Thrombosis and Vascular Biology. Nov 21:1712–1719.Google Scholar
  52. 52.
    Hayden MR, Tyagi SC. 2001. “A” is for amylin and amyloid in type 2 diabetes mellitus. JOP J Pancreas (Online) 2(4):124–139. Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  1. 1.Department of cardiovascular atherosclerosis metabolism and aging Camdenton Community Health CenterCamdentonUSA
  2. 2.FAHA., Deppartment of Physiology and BiophysicsThe University of Mississippi Medical CenterJacksonUSA
  3. 3.Department of Family and Community MedicineUniversity of Missouri-ColumbiaUSA

Personalised recommendations