Secondary prevention of CAD with ACE inhibitors: a struggle between life and death of the endothelium.
Angiotensin-converting enzyme (ACE) inhibitors improve outcomes in patients with coronary artery disease (CAD), heart failure, and hypertension. This short review examines clinical evidence for such effects and the underlying mechanism of action. One potential mode of action for ACE inhibitors in CAD is blood pressure reduction. However, recent data suggest that the effects of ACE inhibitors on the endothelium may also be relevant in attenuating the progression of atherosclerosis. In CAD, chronic overexpression of tissue ACE disrupts the angiotensin II/bradykinin balance with a net result of endothelial dysfunction, mainly due to an increased rate of apoptosis. An imbalance between endothelial apoptosis (death) and its renewal from the bone marrow (life) causes discontinuity of the endothelial layer, favoring the initiation and progression of a biochemical sequence that leads to atherosclerosis, plaque rupture, and eventually acute coronary syndromes. There is clinical and experimental evidence that ACE inhibition improves the life and death cycle of the endothelium. By restoring the bradykinin/angiotensin II balance, ACE inhibition reduces the rate of endothelial apoptosis and experimental results suggest that ACE inhibition can also improve the production and mobilization of endothelial progenitor cells from bone marrow. We report our experience in this context with perindopril.
Ferrari
Roberto
R
Chair of Cardiology, University of Ferrara, Cardiovascular Institute, Arcispedale S. Anna Hospital, C.rso Giovecca 203, Ferrara, 44100, Italy. fri@unife.it
Guardigli
Gabriele
G
Ceconi
Claudio
C
D054058:Acute Coronary Syndrome / Q000517:prevention & control*; D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism; D001920:Bradykinin / Q000187:drug effects / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D020913:Perindopril / Q000627:therapeutic use; D058226:Plaque, Atherosclerotic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D055502:Secondary Prevention; D013234:Stem Cells / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin; D020913:Perindopril