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Secondary Prevention of CAD with ACE Inhibitors: A Struggle Between Life and Death of the Endothelium

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Abstract

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.

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Acknowledgments

The study was supported by a Regional-University project of Emilia Romagna – Area IB – Innovative Research grant.

Conflict of interest

The authors have received honoraria from Servier for being on the Executive Committee of the EUROPA trial and for lectures, and the Foundation Salvatore Maugeri has received research grants from Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity in conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Authors and Affiliations

  1. Chair of Cardiology, University of Ferrara, Cardiovascular Institute, Arcispedale S. Anna Hospital, C.rso Giovecca 203, Ferrara, 44100, Italy

    Roberto Ferrari & Claudio Ceconi

  2. Cardiovascular Research Centre, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy

    Roberto Ferrari & Claudio Ceconi

  3. University Hospital of Ferrara, Ferrara, Italy

    Gabriele Guardigli

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  1. Roberto Ferrari
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  2. Gabriele Guardigli
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Correspondence to Roberto Ferrari.

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Ferrari, R., Guardigli, G. & Ceconi, C. Secondary Prevention of CAD with ACE Inhibitors: A Struggle Between Life and Death of the Endothelium. Cardiovasc Drugs Ther 24, 331–339 (2010). https://doi.org/10.1007/s10557-010-6244-x

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