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

Am J Cardiovasc Drugs. 2011 Jun 1;11(3):189-98. doi: 10.2165/11589400-000000000-00000.

Abstract

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-α 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / physiopathology
  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Antigens, CD34 / metabolism
  • Apoptosis / drug effects
  • Bone Marrow Cells / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Perindopril / pharmacology
  • Single-Blind Method
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Tetrazoles / pharmacology
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Valsartan

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Antigens, CD34
  • Tetrazoles
  • Valsartan
  • Valine
  • Perindopril