ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes

Elisa Cangiano, Jlenia Marchesini, Gianluca Campo, Gloria Francolini, Cinzia Fortini, Giacomo Carr, Matteo Miccoli, Claudio Ceconi, Luigi Tavazzi, Roberto Ferrari

Research output: Contribution to journalArticle

29 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)189-198
Number of pages10
JournalAmerican Journal of Cardiovascular Drugs
Volume11
Issue number3
DOIs
Publication statusPublished - 2011

Fingerprint

Valsartan
Acute Coronary Syndrome
Perindopril
Angiotensin Receptor Antagonists
Apoptosis
Myocardial Infarction
Human Umbilical Vein Endothelial Cells
Bradykinin
Serum
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
Bone Marrow Cells
Vascular Endothelial Growth Factor A
Endothelium
Tumor Necrosis Factor-alpha
Control Groups
Endothelial Progenitor Cells
Therapeutics

Keywords

  • ACE inhibition
  • acute coronary syndromes
  • angiotensin II receptor blocker
  • apoptosis
  • endothelial progenitor cells

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes. / Cangiano, Elisa; Marchesini, Jlenia; Campo, Gianluca; Francolini, Gloria; Fortini, Cinzia; Carr, Giacomo; Miccoli, Matteo; Ceconi, Claudio; Tavazzi, Luigi; Ferrari, Roberto.

In: American Journal of Cardiovascular Drugs, Vol. 11, No. 3, 2011, p. 189-198.

Research output: Contribution to journalArticle

Cangiano, Elisa ; Marchesini, Jlenia ; Campo, Gianluca ; Francolini, Gloria ; Fortini, Cinzia ; Carr, Giacomo ; Miccoli, Matteo ; Ceconi, Claudio ; Tavazzi, Luigi ; Ferrari, Roberto. / ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes. In: American Journal of Cardiovascular Drugs. 2011 ; Vol. 11, No. 3. pp. 189-198.
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T1 - ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes

AU - Cangiano, Elisa

AU - Marchesini, Jlenia

AU - Campo, Gianluca

AU - Francolini, Gloria

AU - Fortini, Cinzia

AU - Carr, Giacomo

AU - Miccoli, Matteo

AU - Ceconi, Claudio

AU - Tavazzi, Luigi

AU - Ferrari, Roberto

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AB - 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.

KW - ACE inhibition

KW - acute coronary syndromes

KW - angiotensin II receptor blocker

KW - apoptosis

KW - endothelial progenitor cells

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