title: Calcitonin gene-related peptide, heme oxygenase-1, endothelial progenitor cells and nitric oxide-dependent vasodilation relationships in a human model of angiotensin II type-1 receptor antagonism.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Medicine, Clinica Medica 4, University of Padova, Padova, Veneto, Italy.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Calò
authors.forename: Paul A
authors.initials: PA
authors.lastname: Davis
authors.forename: Elisa
authors.initials: E
authors.lastname: Pagnin
authors.forename: Lucia
authors.initials: L
authors.lastname: Dal Maso
authors.forename: Paola
authors.initials: P
authors.lastname: Caielli
authors.forename: Gian P
authors.initials: GP
authors.lastname: Rossi
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001477:Bartter Syndrome / Q000378:metabolism / Q000503:physiopathology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D053579:Gitelman Syndrome / Q000378:metabolism / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009569:Nitric Oxide / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing); D015740:Calcitonin Gene-Related Peptide