title: β Integrins mediate FAK Y397 autophosphorylation of resistance arteries during eutrophic inward remodeling in hypertension.
abstract: Human essential hypertension is characterized by eutrophic inward remodeling of the resistance arteries with little evidence of hypertrophy. Upregulation of αVβ3 integrin is crucial during this process. In order to investigate the role of focal adhesion kinase (FAK) activation in this process, the level of FAK Y397 autophosphorylation was studied in small blood vessels from young TGR(mRen2)27 animals as blood pressure rose and eutrophic inward remodeling took place. Between weeks 4 and 5, this process was completed and accompanied by a significant increase in FAK phosphorylation compared with normotensive control animals. Phosphorylated (p)FAK Y397 was coimmunoprecipitated with both β1- and β3-integrin-specific antibodies. In contrast, only a fraction (<10-fold) was coprecipitated with the β3 integrin subunit in control vessels. Inhibition of eutrophic remodeling by cRGDfV treatment of TGR(mRen2)27 rats resulted in the development of smooth-muscle-cell hypertrophy and a significant further enhancement of FAK Y397 phosphorylation, but this time with exclusive coassociation of pFAK Y397 with integrin β1. We established that phosphorylation of FAK Y397 with association with β1 and β3 integrins occurs with pressure-induced eutrophic remodeling. Inhibiting this process leads to an adaptive hypertrophic vascular response induced by a distinct β1-mediated FAK phosphorylation pattern.
authors.affiliation: Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK.
authors.forename: Egidius H J
authors.initials: EH
authors.lastname: Heerkens
authors.forename: Lisa
authors.initials: L
authors.lastname: Quinn
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006973:Hypertension / Q000503:physiopathology*; D039564:Integrin alphaV / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D039661:Integrin beta3 / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D066253:Vascular Remodeling / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D039564:Integrin alphaV; D019012:Integrin beta1; D039661:Integrin beta3; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat