ACE Inhibition Modulates Endothelial Apoptosis and Renewal via Endothelial Progenitor Cells in Patients with Acute Coronary Syndromes
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- Cangiano, E., Marchesini, J., Campo, G. et al. Am J Cardiovasc Drugs (2011) 11: 189. doi:10.2165/11589400-000000000-00000
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The equilibrium between endothelial apoptosis and endothelial renewal is altered in acute coronary syndromes and may be related to differences in the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers).
We evaluated the effect of treatment on endothelial function in post-myocardial infarction (MI) patients treated with perindopril (group 2, n = 16) or valsartan (group 3, n = 17) at baseline and after 7, 15, and 30 days and in normal controls (group 1, n = 20). Endothelial apoptosis was determined by cultivating serum samples in vitro with human umbilical vein endothelial cells (HUVECs), while endothelial renewal was assessed by mobilization of CD34+ bone marrow cells.
At baseline, post-MI patients had significantly elevated rates of apoptosis (16.6±5.0% and 16.5±8.4% in groups 2 and 3, respectively [both p = 0.01] vs 1.6±0.7% in group 1), which declined in group 2 (10.5±4.4% at 30 days, p = 0.04), but not in group 3. Similar results and trends were found for the Bax/Bcl-2 ratio. CD34+ mobilization was significantly increased in group 2 (3.0±1.0 at baseline to 6.2±1.6 at 15 days, p = 0.03), whereas in group 3 CD34+ mobilization did not change significantly. The findings in group 2 were accompanied by an increase in vascular endothelial growth factor at 15 days, and a reduction in tumor necrosis factor-α and its soluble receptors, versus no change in group 3. Similar findings were observed for angiotensin II and bradykinin.
Our results indicate that perindopril, but not valsartan, reduces the proapoptotic effect of serum on the endothelium and increases endothelial renewal in patients with acute coronary syndromes.