Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension
Mobilization of putative high-proliferative-potential endothelial colony-forming cells during antihypertensive treatment in patients with essential hypertension
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DOI：
10.1089/scd.2006.0074
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发表时间：
2007-04-01
影响因子：
4
通讯作者：
Boeger, Rainer
中科院分区：
文献类型：
--
作者：
Benndorf, Ralf A.;Gehling, Ursula M.;Boeger, Rainer
最近的研究表明，在血管损伤或缺血时，骨髓来源的内皮祖细胞(EPC)会被招募到循环中。为探讨降压治疗是否对循环内皮祖细胞数量有影响，对高血压病患者应用血管紧张素受体拮抗剂替米沙坦、钙通道阻滞剂尼索地平或两者联合治疗6周。在基线以及治疗3周和6周后，通过荧光激活细胞分类(FACS)分析和甲基纤维素基分析中内皮祖细胞产生内皮细胞系集落形成单位(CFU-EC)的能力来鉴定和量化内皮祖细胞。在治疗期间，尼索地平组的患者，但替米沙坦组的患者，表现出显著的内皮祖细胞动员，部分有能力产生由1000多个细胞组成的大型集落。此外，CFU-EC的数量与循环中CD133(+)/CD34(+)/CD146(+)细胞的数量显著相关，从而提供了具有该表型的细胞代表功能性内皮祖细胞的有力证据。治疗过程中各时间点CFU-EC数量与血压水平之间无相关性。因此，尼索地平诱导内皮祖细胞的动员可能代表了一种新的机制，这种降压化合物独立于其降压作用而有助于高血压患者的血管保护。
Recent studies have shown that in response to vascular damage or ischemia, bone marrow-derived endothelial progenitor cells (EPCs) are recruited into the circulation. To investigate whether antihypertensive treatment has an influence on the number of circulating EPCs, patients with essential hypertension were treated either with the angiotensin receptor antagonist telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks. At baseline and after 3 and 6 weeks of treatment, EPCs were identified and quantified by fluorescence-activated cell sorting (FACS) analysis and by their capacity to generate colony-forming units of the endothelial lineage (CFU-EC) in a methylcellulose-based assay. During treatment, patients in the nisoldipine groups, but not in the telmisartan group, showed a significant mobilization of EPCs, which in part had the capacity to generate large-sized colonies comprising more than 1,000 cells. Moreover, a remarkable correlation between the number of CFU-EC and the number of circulating CD133(+)/CD34(+)/CD146(+) cells was observed, thereby providing strong evidence that cells with this phenotype represent functional EPCs. No correlation was found between the numbers of CFU-EC and the blood pressure levels at any time point during the treatment. Hence, nisoldipine-induced mobilization of EPCs might represent a novel mechanism by which this antihypertensive compound independently of its blood pressure-lowering effect contributes to vasoprotection in patients with essential hypertension.