Search

Introduction: Circulating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a crucial role in the pathophysiology of coronary artery disease (CAD). Angiotensin II receptor antagonism has been shown to be able to increase EPCs in hypertension but its effect in patients with CAD is unknown. Aim of this study was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can modify the number of subpopulations of EPCs and may in turn affect the endothelial function of normotensive patients with CAD., Methods: In a prospective double-blind parallel group study, 40 normotensive patients with CAD were randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of coronary angiography. Measurements of EPCs and assessment of flow-mediated dilatation (FMD) of the brachial artery was performed before and after therapy., Results: Absolute number of EPCs was similar at baseline in the telmisartan and placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45- cells increased significantly in the telmisartan group (from 0.010+/-0.003 to 0.014+/-0.004%, P=0.0001) but not in the placebo group (from 0.009+/-0.004 to 0.009+/-0.005%, NS). Similarly, CD133+/KDR+/CD45- cells raised significantly with telmisartan (from 0.003+/-0.002 to 0.006+/-0.002%, P=0.0001) but not with placebo (from 0.004+/-0.003 to 0.003+/-0.002%, NS). Also, CD14+/CD45+ cells increased significantly with telmisartan (from 0.005+/-0.002 to 0.008+/-0.002%, P=0.0001) and were unchanged with placebo (0.006+/-0.002 vs. 0.005+/-0.003%, NS). FMD improved significantly in patients who received telmisartan (10.4+/-3.9%, P=0.0015 vs. baseline) but did not change in the placebo group (5.9+/-2.8%; P=0.32 vs. baseline; telmisartan vs. placebo, P=0.002). A significant positive correlation was found in the telmisartan group between the improvement in FMD and the increase in CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (r=0.55, P<0.01, and r=0.49, P<0.05, respectively)., Conclusion: Angiotensin II receptor antagonism with telmisartan increases the number of regenerative EPCs and improves endothelial function in normotensive patients with CAD. These novel effects are interrelated and can explain, at least in part, why telmisartan has beneficial cardiovascular effects independent of its blood pressure lowering action., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis., Background: Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis., Methods: We studied 155 consecutive stable angina patients (92 men, age 60 +/- 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison., Results: At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 +/- 0.64 cells/microl) were significantly higher than in the progression, stable, and control groups (1.03 +/- 0.53 cells/microl, 1.07 +/- 0.46 cells/microl, and 0.95 +/- 0.44 cells/microl, respectively, p < 0.05). Similarly, CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 +/- 0.23 cells/microl) compared with progression, stable, and control groups (0.33 +/- 0.19 cells/microl, 0.41 +/- 0.32 cells/microl, and 0.36 +/- 0.15 cells/microl, respectively, p < 0.001). Also, numbers of CD14+/CD45+ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 +/- 0.56 cells/microl vs. 0.51 +/- 0.52 cells/microl vs. 0.28 +/- 0.54 cells/microl vs. 0.62 +/- 0.67 cells/microl, respectively, p < 0.05), whereas CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups., Conclusions: Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Endothelial progenitor cells (EPCs) play a key role in maintenance of endothelial integrity and postnatal neovascularization. We verified whether the number of subpopulations of EPCs is different in patients with coronary artery disease (CAD) and normal or impaired left ventricular (LV) function., Methods: Sixty-eight consecutive patients (37 men, age 60+/-18 years) with CAD were studied. All patients underwent quantitative coronary angiography and flow cytometric analysis., Results: Patients with LV ejection fraction <45% (n=22) were compared with those with normal function (n=46). The two groups had similar age, sex, cardiovascular risk factors, medical therapy, LV dimension, and number of diseased vessels. Patients with LV dysfunction, by study design, were more symptomatic and had a lower LV ejection fraction. The two groups had similar white cell count and mononuclear cells. The absolute number of CD34 and CD133 cells was significantly (P<0.05) higher in patients with LV dysfunction as compared with patients with normal function or healthy participants. In contrast, CD14 cells were significantly (P=0.005) lower in the former patients than in the latter, whereas no significant difference was noted in the number of cells positive for CD105 among groups., Conclusion: Subpopulations of EPCs have a discordant behavior in CAD patients with or without LV dysfunction, with cells positive for the endothelial markers CD34 and CD133 being increased and cells that promote vasculogenesis and microvascular development being significantly reduced.