Objective: Injury of vascular endothelium, crucial in vascular disease, is repaired via circulating endothelial progenitor cells (cEPCs). In hypertension, cEPCs number is reduced and function impaired adding further risk for cardiovascular (CV) events. Angiotensin II (Ang II)-induced oxidative stress (OxSt), accelerates cEPCs senescence. Calcitonin gene-related peptide (CGRP), able to prevent and reverse Ang II-induced cEPCs senescence, is reduced in hypertension and stimulated by the antioxidant and anti-inflammatory heme oxygenase (HO)-1. In essential hypertensive patients olmesartan reduced OxSt and markers of CV remodeling and increased HO-1. This study reports in essential hypertensive patients the effect of 6 months treatment with olmesartan on plasma level of CGRP and number and survival of cEPCs.
Methods and results: In 20 essential hypertensive patients treated with olmesartan medoxomil (20 mg per day for 6 months), cEPCs (CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+) (direct 3-color flow cytometry analysis), apoptosis of cEPCs (CD133+KDR+ cells with Annexin V expression), CGRP determination (ELISA) and HO-1 protein level (western blot) were assessed at baseline and after 3 and 6 months of treatments. Olmesartan normalized blood pressure (P < 0.001), increased cEPCs from baseline (CD34+KDR+: P < 0.003; CD133+KDR+: P < 0.0002; CD34+CD133+KDR+: P = 0.0008), reduced cEPCs apoptosis (P < 0.001) and increased CGRP (P < 0.013) and HO-1 (P = 0.039).
Conclusion: These results provide a mechanistic rationale for the olmesartan‘s antioxidant and anti-inflammatory potential translation toward antiatherosclerotic and antiremodeling effects reported on clinical ground.
aDepartment of Medicine, Clinica Medica 4
bEmathology and Immunology, University of Padova, Italy
Correspondence to Lorenzo A. Calò, MD, PhD, Department of Medicine, Clinica Medica 4, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel: +39 049 8218701 8212279; fax: +39 049 8754179; e-mail: firstname.lastname@example.org
Abbreviations: BS/GS, Bartter's/Gitelman's syndromes; CGRP, calcitonin gene-related peptide; EPCs, endothelial progenitor cells; HO-1, heme oxygenase-1
Received 22 April, 2013
Revised 28 May, 2013
Accepted 16 July, 2013