Current Atherosclerosis Reports

, Volume 3, Issue 2, pp 117–124

The renin angiotensin system as a risk factor for coronary artery disease

  • John A. Farmer
  • Guillermo Torre-Amione


The renin angiotensin system was demonstrated to play a significant role in the genesis of hypertension and regulation of vascular tone over 100 years ago. The early investigations were subsequently expanded to implicate the renin angiotensin system in a variety of physiologic processes that may play a significant role in the initiation and progression of atherosclerosis. The renin angiotensin system modulates vascular structure and left ventricular hypertrophy via a number of trophic effects. Elevated levels of angiotensin II are associated with the generation of oxidative stress, and may thus play a significant role in the earliest phases of atherosclerosis. The role inflammation plays in atherosclerosis is amplified by the renin angiotensin system via the effects on adhesion molecules, growth factors, and chemoattractant molecules, which modulate the migration of inflammatory cells into the subendothelial space. The effects of angiotensin II, which may be at least partially genetically mediated, have been implicated in epidemiologic and clinical studies as a risk factor for the development of atherosclerosis. This review centers on the potential role that the renin angiotensin system plays as a risk factor for the development of atherosclerosis, and the role of converting enzyme inhibition or angiotensin receptor blockade as a mechanism to decrease the initiation, progression, and clinical consequences of the atherosclerotic process.


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References and Recommended Reading

  1. 1.
    Tigerstedt R, Bergman PG: Nere-Und Kreisluaf. Skandinavisches Archiv fur Phyisologie 1898, 8:223–271.Google Scholar
  2. 2.
    Rigat B, Hubert C, Alhenc-Geals F: An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half of the variance of serum enzyme levels. J Clin Invest 1990, 86:1343.PubMedCrossRefGoogle Scholar
  3. 3.
    Prasad A, Narayanan S, Husain S, et al.: Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition. Circulation 2000, 102:35–41.PubMedGoogle Scholar
  4. 4.
    Anderson TJ, Elstein E, Haber H, Charbonneau F: Comparative study of ACE inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease. J Am Coll Cardiol 2000, 35:60–66.PubMedCrossRefGoogle Scholar
  5. 5.
    Prasad A, Narayanan S, Waclawiw MA, et al.: The insertion/deletion polymorphism of the angiotensin converting enzyme gene determines coronary vascular tone in nitric oxide activity. J Am Coll Cardiol 2000, 36:1597–1986.Google Scholar
  6. 6.
    Makris TK, Stavroulakis GA, Dafni UG, et al.: ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension. Am Heart J 2000, 140:760–765.PubMedCrossRefGoogle Scholar
  7. 7.
    Perticone F, Maio R, Cosco C, et al.: Hypertensive left ventricular remodeling and ACE gene polymorphism. Cardiovasc Res 1999, 43:192–199.PubMedCrossRefGoogle Scholar
  8. 8.
    Andersson B, Blange I, Sylven C: Angiotensin II type 1 receptor gene polymorphism in long-term survival in patients with idiopathic congestive heart failure. Eur J Heart Fail 1999, 1:363–369.PubMedCrossRefGoogle Scholar
  9. 9.
    Keaveney B, McKenzie C, Parish S, et al.: Large-scale test of hypothesised associations between the angiotensin converting enzyme insertion/deletion polymorphism and myocardial infarction in about 5,000 cases and 6,000 controls. International Studies of Infarct Survival (ISIS) collaborators. Lancet 2000, 355:434–442.Google Scholar
  10. 10.
    O’Malley JT, Maslen CL, Illingworth DR: Angiotensin converting enzyme and cardiovascular disease risk. Curr Opin Lipidol 1999, 10:407–415.PubMedCrossRefGoogle Scholar
  11. 11.
    Mancini GP, Henry GC, Macaya C, et al.: Angiotensin converting enzyme inhibition improves endothelial asomotor dysfunction in coronary artery disease. The TREND (Trial on Reversing Endothelial Dysfunction) study. Circulation 1996, 94:258–275.PubMedGoogle Scholar
  12. 12.
    Mancini GB: Long-term use of angiotensin converting enzyme inhibitors to modify endothelial dysfunction: a review of clinical investigations. Clin Invest Med 2000, 23:144–161.PubMedGoogle Scholar
  13. 13.
    Prasad A, Tupas-Habib T, Schenke WH, et al.: Acute and chronic angiotensin I receptor antagonism reverses endothelial dystunction in atherosclerosis. Circulation 2000, 101:2349–2354.PubMedGoogle Scholar
  14. 14.
    Schiffrin EL, Park JB, Intengan HD, Touyz RM: Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation 2000, 101:1653–1659.PubMedGoogle Scholar
  15. 15.
    Cheetham C, Collis J, O’Driscoll G, et al.: Losartan, an angiotensin type-1 receptor antagonist improves endothelial function in non-insulin dependent diabetes. J Am Coll Cardiol 2000, 36:1461–1466.PubMedCrossRefGoogle Scholar
  16. 16.
    Ghiadoni L, Virdis A, Magagna A, et al.: Effect of the angiotensin II type-1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000, 35(1 Pt 2):501–506.PubMedGoogle Scholar
  17. 17.
    Strehlow K, Wassmann S, Bohm M, Nickenig G: Angiotensin AT-1 receptor overexpression in hypercholesterolemia. Ann Med 2000, 32:386–389.PubMedCrossRefGoogle Scholar
  18. 18.
    Nickenig G, Baumer AT, Temur Y, et al.: Statin sensitive disregulated AT-1 receptor function and density in hypercholesterolemic men. Circulation 1999, 100:2131–2134.PubMedGoogle Scholar
  19. 19.
    Schmidt-Ott KM, Kagiyama S, Phillips MI: The multiple actions of angiotensin II in atherosclerosis. Regul Pept 2000, 93:65–77.PubMedCrossRefGoogle Scholar
  20. 20.
    Wojakowski W, Gminski J, Siemianowicz K, et al.: The influence of angiotensin converting enzyme inhibitors on lipid peroxidation in sera and aorta of rabbits in diet induced hypercholesterolemia. Int J Mol Med 2000, 6:591–594.PubMedGoogle Scholar
  21. 21.
    Hayek T, Attias J, Coleman R, et al.: The angiotensin converting enzyme inhibitor fosinopril and the angiotensin receptor antagonist losartan inhibit LDL oxidation and attenuate atherosclerosis independent of blood pressure lowering in apolipoprotein E deficient mice. Cardiovasc Res 1999, 44:579–587.PubMedCrossRefGoogle Scholar
  22. 22.
    Hayek T, Aviram M, Heinrich R, et al.: Losartan inhibits cellular uptake of oxidized LDL by monocyte-macrophages from hypercholesterolemic patients. Biochem Biophys Res Commun 2000, 273:417–420.PubMedCrossRefGoogle Scholar
  23. 23.
    Strawn WB, Chappell MC, Dean RH, et al.: Inhibition of early atherogenesis by losartan in monkeys with diet induced hypercholesterolemia. Circulation 2000, 101:1586–1593.PubMedGoogle Scholar
  24. 24.
    Seeger H, Mueck AO, Lippert TH: Effects of valsartan in 17-beta estradial on the oxidation of low density lipoprotein in vitro. Coronary Artery Dis 2000, 11:347–349.CrossRefGoogle Scholar
  25. 25.
    Yusuf S, Dagenais G, Pogue J, et al.: Vitamin E supplementation and cardiovascular events in high risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:154–160.PubMedCrossRefGoogle Scholar
  26. 26.
    Schnee JM, Hsueh WA: Angiotensin II adhesion and cardiac fibrosis. Cardiovasc Res 2000, 46:264–268.PubMedCrossRefGoogle Scholar
  27. 27.
    Kranzhofer R, Schmidt J, Pfeiffer CA, et al.: Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999, 19:1623–1629.PubMedGoogle Scholar
  28. 28.
    Ruiz-Ortega M, Lorenzo O, Ruperez M, et al.: Angiotensin II activates nuclear transcription factor kappa C through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanism. Circ Res 2000, 86:1266–1272.PubMedGoogle Scholar
  29. 29.
    Ridker PM, Rifai N, Stampfer MJ, Hennekens CH: Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000, 101:1767–1772.PubMedGoogle Scholar
  30. 30.
    Ridker PM, Rifai N, Pfeffer M, et al.: Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000, 101:2149–2153.PubMedGoogle Scholar
  31. 31.
    McTiernan CF, Feldman SR: The role of tumor necrosis factor alpha in the pathophysiology of congestive heart failure. Curr Cardiol Rep 2000, 2:189–197.PubMedCrossRefGoogle Scholar
  32. 32.
    Ridker PM, Rifai N, Pfeffer M, et al.: Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000, 101:2149–2153.PubMedGoogle Scholar
  33. 33.
    Lindahl B, Toss H, Siegbahn A, et al.: Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary disease. FRISC Study Group. N Engl J Med 2000, 343:1139–1147.PubMedCrossRefGoogle Scholar
  34. 34.
    Ridker PM, Glynn RJ, Hennekens CH: C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998, 97:2007–2011.PubMedGoogle Scholar
  35. 35.
    Ridker PM, Rifai N, Pfeffer MA, et al.: Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) SInvestigators. Circulation 1999, 100:230–235.PubMedGoogle Scholar
  36. 36.
    Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000, 342:836–843.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2001

Authors and Affiliations

  • John A. Farmer
    • 1
  • Guillermo Torre-Amione
    • 1
  1. 1.Section of CardiologyBen Taub General Hospital and Baylor College of MedicineHoustonUSA

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