替米沙坦的血管紧张素 II 受体拮抗作用可增加冠状动脉疾病的血压正常患者内皮祖细胞的数量：一项随机、双盲、安慰剂对照研究。

Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: a randomized, double-blind, placebo-controlled study.

机构信息

Department of Cardiovascular Diseases, San Filippo Neri Hospital, and Department Attilio Reale, Sapienza University, Rome, Italy.

出版信息

Atherosclerosis. 2010 Jun;210(2):510-5. doi: 10.1016/j.atherosclerosis.2009.12.005. Epub 2009 Dec 11.

DOI:10.1016/j.atherosclerosis.2009.12.005

PMID:20044087

Abstract

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.

摘要

简介

循环内皮祖细胞（EPCs）为功能失调的内皮提供了一种内源性修复机制，因此在冠状动脉疾病（CAD）的病理生理学中起着至关重要的作用。已经证明血管紧张素 II 受体拮抗剂能够增加高血压患者的 EPCs，但在 CAD 患者中的作用尚不清楚。本研究的目的是评估血管紧张素 II 受体拮抗剂替米沙坦是否可以改变 EPC 亚群的数量，并可能反过来影响 CAD 正常血压患者的内皮功能。

方法

在一项前瞻性、双盲平行组研究中，40 名正常血压的 CAD 患者在冠状动脉造影时随机接受替米沙坦（80mg）或安慰剂治疗 4 周。在治疗前后分别测量 EPCs 和肱动脉血流介导的舒张功能（FMD）。

结果

替米沙坦组和安慰剂组的 EPC 绝对值在基线时相似。治疗 4 周后，替米沙坦组 CD34+/KDR+/CD45-细胞显著增加（从 0.010+/-0.003 增加至 0.014+/-0.004%，P=0.0001），而安慰剂组则无变化（从 0.009+/-0.004 增加至 0.009+/-0.005%，NS）。同样，CD133+/KDR+/CD45-细胞也随着替米沙坦而显著增加（从 0.003+/-0.002 增加至 0.006+/-0.002%，P=0.0001），而安慰剂组则无变化（从 0.004+/-0.003 增加至 0.003+/-0.002%，NS）。此外，CD14+/CD45+细胞也随着替米沙坦而显著增加（从 0.005+/-0.002 增加至 0.008+/-0.002%，P=0.0001），而安慰剂组则无变化（从 0.006+/-0.002 增加至 0.005+/-0.003%，NS）。替米沙坦组的 FMD 显著改善（10.4+/-3.9%，P=0.0015 与基线相比），而安慰剂组则无变化（5.9+/-2.8%；P=0.32 与基线相比；替米沙坦与安慰剂相比，P=0.002）。在替米沙坦组中，FMD 的改善与 CD34+/KDR+/CD45-细胞和 CD133+/KDR+/CD45-细胞的增加之间存在显著的正相关（r=0.55，P<0.01 和 r=0.49，P<0.05）。