title: Hypertension alters phosphorylation of VASP in brain endothelial cells.
abstract: Hypertension impairs cerebral vascular function. Vasodilator-stimulated phosphoprotein (VASP) mediates active reorganization of the cytoskeleton via membrane ruffling, aggregation and tethering of actin filaments. VASP regulation of endothelial barrier function has been demonstrated by studies using VASP(-/-) animals under conditions associated with tissue hypoxia. We hypothesize that hypertension regulates VASP expression and/or phosphorylation in endothelial cells, thereby contributing to dysfunction in the cerebral vasculature. Because exercise has direct and indirect salutary effects on vascular systems that have been damaged by hypertension, we also investigated the effect of exercise on maintenance of VASP expression and/or phosphorylation. We used immunohistochemistry, Western blotting and immunocytochemistry to examine the effect of hypertension on VASP expression and phosphorylation in brain endothelial cells in normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive (SH) rats under normal and exercise conditions. In addition, we analyzed VASP regulation in normoxia- and hypoxia-induced endothelial cells. Brain endothelial cells exhibited significantly lower VASP immunoreactivity and phosphorylation at the Ser157 residue in SHR versus WKY rats. Exercise reversed hypertension-induced alterations in VASP phosphorylation. Western blotting and immunocytochemistry indicated reduction in VASP phosphorylation in hypoxic versus normoxic endothelial cells. These results suggest that diminished VASP expression and/or Ser157 phosphorylation mediates endothelial changes associated with hypertension and exercise may normalize these changes, at least in part, by restoring VASP phosphorylation.
authors.affiliation: 1Department of Neurology, Baskent University Faculty of Medicine, Ankara.
authors.forename: Zulfikar
authors.initials: Z
authors.lastname: Arlier
authors.forename: Murat
authors.initials: M
authors.lastname: Basar
authors.forename: Erdogan
authors.initials: E
authors.lastname: Kocamaz
authors.forename: Kemal
authors.initials: K
authors.lastname: Kiraz
authors.forename: Gamze
authors.initials: G
authors.lastname: Tanriover
authors.forename: Gunnur
authors.initials: G
authors.lastname: Kocer
authors.forename: Sefa
authors.initials: S
authors.lastname: Arlier
authors.forename: Semih
authors.initials: S
authors.lastname: Giray
authors.forename: Seher
authors.initials: S
authors.lastname: Nasırcılar
authors.forename: Filiz
authors.initials: F
authors.lastname: Gunduz
authors.forename: Umit K
authors.initials: UK
authors.lastname: Senturk
authors.forename: Necdet
authors.initials: N
authors.lastname: Demir
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D005081:Exercise Therapy; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000534:rehabilitation; D000860:Hypoxia / Q000503:physiopathology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012694:Serine / Q000378:metabolism; D018709:Statistics, Nonparametric; D013550:Swimming; D013997:Time Factors; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; D012694:Serine; D010100:Oxygen
keywords: NO; VASP; hypertension; vascular endothelial cell