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.

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.

• Authors: Lorenzo A Calò, Paul A Davis, Elisa Pagnin, Lucia Dal Maso, Paola Caielli, Gian P Rossi
• Journal: Journal of hypertension (J Hypertens) Vol. 30 Issue 7 Pg. 1406-13 (Jul 2012) ISSN: 1473-5598 [Electronic] England
• PMID: 22573121 (Publication Type: Journal Article)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Nitric Oxide
• Heme Oxygenase (Decyclizing)
• Calcitonin Gene-Related Peptide

Topics

• Adult
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Bartter Syndrome (metabolism, physiopathology)
• Calcitonin Gene-Related Peptide (metabolism)
• Cohort Studies
• Endothelium, Vascular (pathology)
• Female
• Gitelman Syndrome (metabolism, physiopathology)
• Heme Oxygenase (Decyclizing) (metabolism)
• Humans
• Male
• Middle Aged
• Models, Biological
• Nitric Oxide (physiology)
• Stem Cells (pathology)
• Vasodilation (physiology)