AKT participates in endothelial dysfunction in hypertension(339 views) Iaccarino G, Ciccarelli M, Sorriento D, Cipolletta E, Cerullo V, Iovino GL, Paudice A, Elia A, Santulli G, Campanile A, Arcucci O, Pastore L, Salvatore F, Condorelli G, Trimarco B
Department of Clinical Medicine, University of Naples Federico II, Italy
Dept. of Biochem. and Med. Biotech., University of Naples Federico II, Italy
School of Biotechnologican Sciences, University of Naples Federico II, Italy
CEINGE-Biotecnologie Avanzate, Naples, Italy
San Raffaele Biomedical Science Park, Rome, Italy
Medicina Clinica, Sci. Cardiovasc. ed Immunologiche, Federico II University, Via Pansini 5, 80131 Naples, Italy
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AKT participates in endothelial dysfunction in hypertension
Background - In hypertension, reduced nitric oxide production and blunted endothelial vasorelaxation are observed. It was recently reported that AKT phosphorylates and activates endothelial nitric oxide synthase and that impaired kinase activity may be involved in endothelial dysfunction. Methods and Results - To identify the physiological role of the kinase in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), we used adenoviral vectors to transfer the human AKTI gene selectively to the common carotid endothelium. In vitro, endothelial vasorelaxations to acetylcholine, isoproterenol, and insulin were blunted in control carotids from SHR compared with WKY rats, and human AKT1 overexpression corrected these responses. Similarly, blood flow assessed in vivo by Doppler ultrasound was reduced in SHR compared with WKY carotids and normalized after AKT1 gene transfer. In primary cultured endothelial cells, we evaluated AKT phosphorylation, activity, and compartmentalization and observed a mislocalization of the kinase in SHR. Conclusions - We conclude that AKT participates in the settings of endothelial dysfunction in SHR rats by impaired membrane localization. Our data suggest that AKT is involved in endothelium dysfunction in hypertension.
AKT participates in endothelial dysfunction in hypertension
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