αV Integrins Are Necessary for Eutrophic Inward Remodeling of Small Arteries in Hypertension

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Abstract
Human essential hypertension is characterized by eutrophic remodeling of small arteries, with little evidence of hypertrophy. Likewise, vessels of young hypertensive TGR(mRen2)27 animals have undergone similar structural alterations. The role of integrins in resistance arteries of TGR(mRen2)27 during the eutrophic-remodeling process was examined as blood pressure rose. Initially, 8 α and 3 β integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only αV was significantly raised. In conjunction, we confirmed elevated integrin αV protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. β1 and β3, but not β5 integrin subunits were coprecipitated with integrin αV and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of αVβ3 abolished remodeling but enhanced growth, indicating that hypertrophy supervened as a response to hypertension-induced increases in wall stress. We have established that the only upregulated integrin, the αV subunit of integrin αVβ3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific αVβ3-extracellular matrix interactions are likely to allow vascular smooth muscle cell–length autoregulation, which includes a migratory process, to maintain a narrowed lumen after a prolonged constricted state.