title: Endothelial progenitor cells relationships with clinical and biochemical factors in a human model of blunted angiotensin II signaling.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Clinica Medica 4, School of Medicine, University of Padova, Padova, Italy. renzcalo@unipd.it
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Calò
authors.forename: Monica
authors.initials: M
authors.lastname: Facco
authors.forename: Paul A
authors.initials: PA
authors.lastname: Davis
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Lucia Dal
authors.initials: LD
authors.lastname: Maso
authors.forename: Massimo
authors.initials: M
authors.lastname: Puato
authors.forename: Paola
authors.initials: P
authors.lastname: Caielli
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Achille C
authors.initials: AC
authors.lastname: Pessina
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000804:Angiotensin II / Q000502:physiology*; D015703:Antigens, CD / Q000502:physiology; D018952:Antigens, CD34 / Q000502:physiology; D001477:Bartter Syndrome / Q000235:genetics / Q000503:physiopathology*; D001916:Brachial Artery / Q000502:physiology / Q000503:physiopathology; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D053579:Gitelman Syndrome / Q000235:genetics / Q000503:physiopathology*; D006023:Glycoproteins / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D010455:Peptides / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000804:Angiotensin II; D009569:Nitric Oxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D040301:Vascular Endothelial Growth Factor Receptor-2