Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling

• Published in: Hypertension research Vol. 34; no. 9; pp. 1017 - 1022
• Main Authors: Calò, Lorenzo A, Facco, Monica, Davis, Paul A, Pagnin, Elisa, Maso, Lucia Dal, Puato, Massimo, Caielli, Paola, Agostini, Carlo, Pessina, Achille C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2011
• Subjects: 631/443/592; 631/532; 631/80/86/2363; AC133 Antigen; Adult; Angiotensin II - physiology; Antigens, CD - physiology; Antigens, CD34 - physiology; Bartter Syndrome - genetics; Bartter Syndrome - physiopathology; Brachial Artery - physiology; Brachial Artery - physiopathology; cardiovascular remodeling; Endothelial Cells - physiology; EPC; Female; Geriatrics/Gerontology; Gitelman Syndrome - genetics; Gitelman Syndrome - physiopathology; Glycoproteins - physiology; Health Promotion and Disease Prevention; heme oxygenase-1; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - physiology; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; nitric oxide; Nitric Oxide - physiology; Obstetrics/Perinatology/Midwifery; original-article; Peptides - physiology; Public Health; Signal Transduction; Stem Cells - physiology; Vascular Endothelial Growth Factor Receptor-2 - physiology; Vasodilation - physiology; EPC; nitric oxide; heme oxygenase-1; cardiovascular remodeling
• ISSN: 0916-9636; 1348-4214; 1348-4214
• DOI: 10.1038/hr.2011.72

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.