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: Lorenzo A Calò, Monica Facco, Paul A Davis, Elisa Pagnin, Lucia Dal Maso, Massimo Puato, Paola Caielli, Carlo Agostini, Achille C Pessina
• Journal: Hypertension research : official journal of the Japanese Society of Hypertension (Hypertens Res) Vol. 34 Issue 9 Pg. 1017-22 (Sep 2011) ISSN: 1348-4214 [Electronic] England
• PMID: 21654754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AC133 Antigen
• Antigens, CD
• Antigens, CD34
• Glycoproteins
• PROM1 protein, human
• Peptides
• Angiotensin II
• Nitric Oxide
• HMOX1 protein, human
• Heme Oxygenase-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• AC133 Antigen
• Adult
• Angiotensin II (physiology)
• Antigens, CD (physiology)
• Antigens, CD34 (physiology)
• Bartter Syndrome (genetics, physiopathology)
• Brachial Artery (physiology, physiopathology)
• Endothelial Cells (physiology)
• Female
• Gitelman Syndrome (genetics, physiopathology)
• Glycoproteins (physiology)
• Heme Oxygenase-1 (genetics, physiology)
• Humans
• Male
• Middle Aged
• Nitric Oxide (physiology)
• Peptides (physiology)
• Signal Transduction
• Stem Cells (physiology)
• Vascular Endothelial Growth Factor Receptor-2 (physiology)
• Vasodilation (physiology)