OBJECTIVE: An increased number of endothelial progenitor cells (EPCs), which correlated with heme oxygenase-1 gene expression and nitric oxide-mediated vasodilation [flow-mediated dilation (FMD)], has been recently reported by us in Bartter/Gitelman syndromes, rare diseases that represent a human model of endogenous angiotensin (Ang) II type-1 receptor antagonism and depicting an opposite picture of hypertension. Calcitonin gene-related peptide (CGRP), which prevents circulating EPCs senescence and reverses Ang II-induced EPCs senescence is reduced in hypertensive patients, its level is stimulated by heme oxygenase-1 and is related with stimulation of nitric oxide. This study reports on CGRP concentration and heme oxygenase-1 protein level in Bartter/Gitelman syndrome's patients compared with healthy individuals and analyzes their relationships with EPCs [CD34⁺kinase insert domain receptor (KDR⁺), CD133⁺KDR⁺, CD34⁺CD133⁺KDR⁺) as well as FMD. METHODS AND RESULTS: CGRP concentration (ELISA) and heme oxygenase-1 protein level (sandwich immunoassay) were higher in Bartter/Gitelman syndrome : 38.20 ± 8.23 pg/ml vs. 25.07 ± 3.51, P < 0.002 and 9.44 ± 3.1 ng/ml vs. 5.52 ± 1.1, P < 0.007, respectively. CD133⁺KDR⁺ and CD34⁺CD133⁺KDR⁺ (direct three-color flow cytometry analysis) and FMD (B-mode echo scan of brachial artery) were confirmed higher in Bartter/Gitelman syndrome. CGRP and heme oxygenase-1 strongly correlated (P < 0.0001) and did not differ by group. In Bartter/Gitelman syndrome, both CGRP and heme oxygenase-1 were strongly correlated with both EPCs and FMD. CONCLUSIONS: Using a human model opposite to hypertension, this study provides information on the relationships between CGRP, heme oxygenase-1, FMD, major clinical and biochemical factors involved in cardiovascular disease, and EPC-specific populations and may also serve to confirm the utility of Bartter/Gitelman syndrome patients in delineating EPCs and related factors roles in the pathophysiology of cardiovascular remodeling in humans.
OBJECTIVE: An increased number of endothelial progenitor cells (EPCs), which correlated with heme oxygenase-1 gene expression and nitric oxide-mediated vasodilation [flow-mediated dilation (FMD)], has been recently reported by us in Bartter/Gitelman syndromes, rare diseases that represent a human model of endogenous angiotensin (Ang) II type-1 receptor antagonism and depicting an opposite picture of hypertension. Calcitonin gene-related peptide (CGRP), which prevents circulating EPCs senescence and reverses Ang II-induced EPCs senescence is reduced in hypertensivepatients, its level is stimulated by heme oxygenase-1 and is related with stimulation of nitric oxide. This study reports on CGRP concentration and heme oxygenase-1 protein level in Bartter/Gitelman syndrome'spatients compared with healthy individuals and analyzes their relationships with EPCs [CD34⁺kinase insert domain receptor (KDR⁺), CD133⁺KDR⁺, CD34⁺CD133⁺KDR⁺) as well as FMD. METHODS AND RESULTS:CGRP concentration (ELISA) and heme oxygenase-1 protein level (sandwich immunoassay) were higher in Bartter/Gitelman syndrome : 38.20 ± 8.23 pg/ml vs. 25.07 ± 3.51, P < 0.002 and 9.44 ± 3.1 ng/ml vs. 5.52 ± 1.1, P < 0.007, respectively. CD133⁺KDR⁺ and CD34⁺CD133⁺KDR⁺ (direct three-color flow cytometry analysis) and FMD (B-mode echo scan of brachial artery) were confirmed higher in Bartter/Gitelman syndrome. CGRP and heme oxygenase-1 strongly correlated (P < 0.0001) and did not differ by group. In Bartter/Gitelman syndrome, both CGRP and heme oxygenase-1 were strongly correlated with both EPCs and FMD. CONCLUSIONS: Using a human model opposite to hypertension, this study provides information on the relationships between CGRP, heme oxygenase-1, FMD, major clinical and biochemical factors involved in cardiovascular disease, and EPC-specific populations and may also serve to confirm the utility of Bartter/Gitelman syndromepatients in delineating EPCs and related factors roles in the pathophysiology of cardiovascular remodeling in humans.
Authors: Lorenzo A Calò; Carmine Savoia; Paul A Davis; Elisa Pagnin; Verdiana Ravarotto; Giuseppe Maiolino Journal: Int J Clin Exp Med Date: 2015-05-15
Authors: Maria Sambataro; Elena Seganfreddo; Fabio Canal; Anna Furlan; Laura Del Pup; Monia Niero; Agostino Paccagnella; Filippo Gherlinzoni; Angelo Paolo Dei Tos Journal: Int J Vasc Med Date: 2014-02-03
Authors: Lorenzo A Calò; Paul A Davis; Giuseppe Maiolino; Elisa Pagnin; Verdiana Ravarotto; Elena Naso; Gianni Carraro; Agostino Naso Journal: Cardiorenal Med Date: 2015-09-17 Impact factor: 2.041
Authors: Katarzyna Magierowska; Dagmara Wojcik; Anna Chmura; Dominik Bakalarz; Mateusz Wierdak; Slawomir Kwiecien; Zbigniew Sliwowski; Tomasz Brzozowski; Marcin Magierowski Journal: Int J Mol Sci Date: 2018-09-28 Impact factor: 5.923