Cell biology and genetics of angiotensin in cardiovascular disease.

GROWTH-PROMOTING EFFECTS OF ANGIOTENSIN: Angiotensin, a vasoconstrictive peptide, is now known to be an agent of vascular and cardiac growth and may directly influence the pathophysiology of coronary artery disease and ventricular remodeling. Vascular growth occurs when angiotensin activates autocrine and paracrine growth factors, including fibroblast growth factor, transforming growth factor beta-1 and platelet-derived growth factor, and is modulated by endothelium-derived vasodilators and growth inhibitors. ANGIOTENSIN AND CARDIOVASCULAR DISEASE: The presence of angiotensin converting enzyme (ACE) and angiotensin II has been demonstrated in vascular tissue, and these local substances are causally involved in the development of vascular lesions. Similarly, angiotensin can stimulate cardiac myocyte growth and matrix modulation. Cardiac tissue ACE is implicated in ventricular remodeling in the course of progressive heart failure. A genetic variant of the ACE gene has been reported to be associated with increased risks of cardiovascular pathology. ACE INHIBITOR THERAPY: To date, studies of ACE inhibitor treatment in human patients have not demonstrated any prevention of restenosis after angioplasty. However, recent clinical trials in postmyocardial infarction reported that ACE inhibitor therapy reduces recurrent myocardial infarction and prevents cardiac enlargement. Long-term prospective trials are currently being conducted to examine the effects of ACE inhibitor therapy on coronary ischemic events and coronary atherosclerosis, as evaluated by angiography or intravascular ultrasound, and the relationship between coronary events and ACE gene polymorphism.

Duke Scholars

Author Victor J. Dzau Medicine, Cardiology