AIM: An imbalance between endothelial apoptosis and regeneration is one of the initiating events in atherosclerosis. Angiotensin-converting enzyme (ACE) inhibition corrects the endothelial dysfunction observed in coronary artery disease, and this could be the consequence of a reduction in the rate of endothelial apoptosis. The aim of this study was to investigate the effect of different ACE inhibitors on endothelial apoptosis. METHODS: We examined the effect of five ACE inhibitors (enalapril, perindopril, quinapril, ramipril, and trandolapril) on the rate of endothelial apoptosis, either in vitro in human umbilical vein endothelial cells (HUVECs), using a serum deprivation method to induce apoptosis, or in vivo in rats, inducing apoptosis via endotoxic shock with Escherichia coli lipopolysaccharides (LPS). RESULTS: We were unable to detect any significant effect of ACE inhibition on the rate of in vitro endothelial apoptosis at concentrations ranging from 5 x 10(-8) to 10(-6) M. In contrast, chronic in vivo administration of ACE inhibitors to rats at dosages that had similar hypotensive effects reduced the rate of LPS-induced apoptosis significantly for perindopril (P < 0.001) and nonsignificantly for the other ACE inhibitors. The order of potency of the ACE inhibitors tested was perindopril > ramipril >> quinapril = trandolapril = enalapril, with significant differences between perindopril and quinapril (P < 0.01), trandolapril (P < 0.001), and enalapril (P < 0.001). The difference between perindopril and ramipril did not reach significance. CONCLUSION: Our experiments suggest differences between ACE inhibitors in terms of inhibition of endothelial apoptosis in vivo.

Differences in the effect of angiotensin-converting enzyme inhibitors on the rate of endothelial cell apoptosis: in vitro and in vivo studies

CECONI, Claudio;FERRARI, Roberto
2007

Abstract

AIM: An imbalance between endothelial apoptosis and regeneration is one of the initiating events in atherosclerosis. Angiotensin-converting enzyme (ACE) inhibition corrects the endothelial dysfunction observed in coronary artery disease, and this could be the consequence of a reduction in the rate of endothelial apoptosis. The aim of this study was to investigate the effect of different ACE inhibitors on endothelial apoptosis. METHODS: We examined the effect of five ACE inhibitors (enalapril, perindopril, quinapril, ramipril, and trandolapril) on the rate of endothelial apoptosis, either in vitro in human umbilical vein endothelial cells (HUVECs), using a serum deprivation method to induce apoptosis, or in vivo in rats, inducing apoptosis via endotoxic shock with Escherichia coli lipopolysaccharides (LPS). RESULTS: We were unable to detect any significant effect of ACE inhibition on the rate of in vitro endothelial apoptosis at concentrations ranging from 5 x 10(-8) to 10(-6) M. In contrast, chronic in vivo administration of ACE inhibitors to rats at dosages that had similar hypotensive effects reduced the rate of LPS-induced apoptosis significantly for perindopril (P < 0.001) and nonsignificantly for the other ACE inhibitors. The order of potency of the ACE inhibitors tested was perindopril > ramipril >> quinapril = trandolapril = enalapril, with significant differences between perindopril and quinapril (P < 0.01), trandolapril (P < 0.001), and enalapril (P < 0.001). The difference between perindopril and ramipril did not reach significance. CONCLUSION: Our experiments suggest differences between ACE inhibitors in terms of inhibition of endothelial apoptosis in vivo.
2007
Ceconi, Claudio; G., Francolini; D., Bastianon; G. L., Gitti; L., Comini; Ferrari, Roberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/524594
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