Department of Clinical and Experimental Medicine, Clinica Medica 4, School of Medicine, University of Padova, Padova, Italy.
Hypertens Res. 2011 Sep;34(9):1017-22. doi: 10.1038/hr.2011.72. Epub 2011 Jun 9.
Angiotensin II (Ang II) is essential for endothelial progenitor cells (EPCs) function as Ang-II-induced oxidative stress causes senescence of EPCs and endothelial dysfunction and Ang II type 1 receptor blockers increase EPCs. Moreover, EPCs activity is dependent on nitric oxide (NO) and heme oxygenase (HO)-1 as these correlate with EPCs senescence and are reduced in hypertensives. Bartter's/Gitelman's syndrome patients (BS/GS), have increased Ang II yet normo/hypotension along with blunted Ang II signaling, reduced oxidative stress, increased NO and HO-1, thus presenting a unique system to explore EPC biology and its relationship with vascular clinical and biochemical correlates. Circulating EPCs, NO-dependent vasodilation (flow-mediated dilation (FMD)) and HO-1 gene expression were characterized in 10 BS/GS patients and in 10 normotensive subjects. EPCs defined by cell surface antigens CD34+kinase-insert domain receptor (KDR+), CD133+KDR+ and CD133+CD34+KDR+ cells were quantitiated via direct three-color flow-cytometry analysis, HO-1 gene expression by reverse transcription-PCR and FMD by B-mode echo scan of the right brachial artery. Correlation analysis was carried out regarding FMD and EPCs, FMD and HO-1 and EPCs and HO-1. In BS/GS, CD34+KDR+ cell numbers did not differ from controls while CD133+KDR+ and CD133+CD34+KDR+ cell numbers were higher. HO-1 gene expression, as well as FMD, was higher in BS/GS compared with controls. Both CD133+KDR+ and CD133+CD34+KDR+ strongly correlated with both FMD and HO-1. FMD and HO-1 were also strongly correlated. These results document in a human system that EPC numbers and specific populations are related to important clinical and biochemical factors involved in cardiovascular (CV) status and reaffirm the utility of BS/GS patients as a useful system to investigate EPC's role(s) in the pathophysiology of cardiovascular remodeling in humans.
血管紧张素 II（Ang II）对内皮祖细胞（EPCs）的功能至关重要，因为 Ang II 诱导的氧化应激导致 EPCs 衰老和内皮功能障碍，而 Ang II 型 1 受体阻滞剂则增加 EPCs。此外，EPCs 的活性依赖于一氧化氮（NO）和血红素加氧酶-1（HO-1），因为这些与 EPCs 衰老有关，并且在高血压患者中减少。巴特氏/吉特曼综合征患者（BS/GS）的 Ang II 增加，但血压正常/降低，同时 Ang II 信号减弱，氧化应激减少，NO 和 HO-1 增加，因此提供了一个独特的系统来探索 EPC 生物学及其与血管临床和生化相关性的关系。在 10 名 BS/GS 患者和 10 名血压正常的受试者中，对循环 EPCs、NO 依赖性血管扩张（血流介导的扩张（FMD））和 HO-1 基因表达进行了特征描述。通过直接三色流式细胞术分析，用 CD34+kinase-insert 域受体（KDR+）、CD133+KDR+和 CD133+CD34+KDR+细胞表面抗原定义 EPCs，通过逆转录-PCR 测定 HO-1 基因表达，通过右肱动脉 B 型超声扫描测定 FMD。进行了 FMD 与 EPCs、FMD 与 HO-1 和 EPCs 与 HO-1 之间的相关性分析。在 BS/GS 中，CD34+KDR+细胞数量与对照组无差异，而 CD133+KDR+和 CD133+CD34+KDR+细胞数量较高。与对照组相比，BS/GS 中的 HO-1 基因表达和 FMD 更高。CD133+KDR+和 CD133+CD34+KDR+均与 FMD 和 HO-1 强烈相关。FMD 和 HO-1 也强烈相关。这些结果在人类系统中证明，EPC 数量和特定群体与心血管（CV）状态中涉及的重要临床和生化因素有关，并再次证实 BS/GS 患者作为研究 EPC 在人类心血管重塑病理生理学中作用的有用系统的效用。
