The
biological actions of
angiotensin II (ANG), the most prominent
hormone of the renin-angiotensin-aldosterone system (RAAS), may promote the development of
atherosclerosis in many ways. ANG aggravates
hypertension,
metabolic syndrome, and endothelial dysfunction, and thereby constitutes a major risk factor for
cardiovascular disease. The formation of atherosclerotic lesions involves local uptake, synthesis and oxidation of
lipids,
inflammation, as well as cellular migration and proliferation--mechanisms that may all be enhanced by ANG via its AT1 receptor. ANG may also increase the risk of acute
thrombosis by destabilizing
atherosclerotic plaques and enhancing the activity of thrombocytes and coagulation. After
myocardial infarction, ANG promotes myocardial remodeling and
fibrosis, and its many pathological mechanisms deteriorate the prognosis of these high-risk patients in particular. Therapeutically, inhibitors of the
angiotensin I-converting enzyme (ACEI) and AT1 receptor blockers (ARB) are available to suppress the generation and cellular signaling of ANG, respectively. Despite major differences in the efficacy of ANG suppression and the modulation of other
hormones and receptors, both classes of drugs are generally effective in attenuating numerous pathomechanisms of ANG in vitro, and in diminishing the development of atherosclerotic lesions and restenosis after angioplasty in various animal models. In clinical
therapy, ACEI and ACE are well-tolerated
antihypertensive drugs that also improve the prognosis of
heart failure patients. After
myocardial infarction and in stable
coronary heart disease, ACEI have been shown to reduce mortality in a manner independent of hemodynamic alterations. However, there is little evidence that inhibitors of the RAAS may be effective against arterial restenosis, and a possible benefit of these substances compared to other
antihypertensive drugs in the primary prevention of
coronary heart disease in hypertensive patients is still a matter of debate, possibly depending on the specific substance and condition being investigated. As such, the general clinical efficacy of ACEI and ARB may be due to a positive influence on hemodynamic load, vascular function, myocardial remodeling, and neuro-humoral regulation, rather than to a direct attenuation of the atherosclerotic process. Further therapeutic advances may be achieved by identifying optimum drugs, patient populations, and treatment protocols.