Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling
Calò LA, Facco M, Davis PA, Pagnin E, Maso LD, Puato M, Caielli P, Agostini C, Pessina AC.
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.