ACE Inhibition Modulates Endothelial Apoptosis and Renewal via Endothelial Progenitor Cells in Patients with Acute Coronary Syndromes

作者:Cangiano Elisa; Marchesini Jlenia; Campo Gianluca; Francolini Gloria; Fortini Cinzia; Carra Giacomo; Miccoli Matteo; Ceconi Claudio; Tavazzi Luigi; Ferrari Roberto*
来源:American Journal of Cardiovascular Drugs, 2011, 11(3): 189-198.
DOI:10.2165/11589400-000000000-00000

摘要

Background: 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).
Methods: 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.
Results: 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-a and its soluble receptors, versus no change in group 3. Similar findings were observed for angiotensin II and bradykinin.
Conclusion: 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.

  • 出版日期2011