Published Online
on December 27, 2005

A more recent version of this article appeared on February 1, 2006

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Submitted on July 8, 2005
Revised on July 25, 2005

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

Egidius H.J. Heerkens; Linda Shaw; Alisdair Ryding; Gillian Brooker; John J. Mullins; Clare Austin; Vasken Ohanian; and Anthony M. Heagerty^*

From the Department of Medicine (E.H.J.H., L.S., C.A., V.O., A.M.H.), University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom; and Molecular Physiology Group A.R., G.B., J.J.M.), University of Edinburgh, Edinburgh, Midlothian, United Kingdom.

^* To whom correspondence should be addressed. E-mail: tony.heagerty{at}man.ac.uk.

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 and 3 integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only V was significantly raised. In conjunction, we confirmed elevated integrin V protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. 1 and 3, but not 5 integrin subunits were coprecipitated with integrin V and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of V3 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 V subunit of integrin V3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific V3-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.

Key words: integrins • hypertrophy • hypertension • extracellular matrix

Related Article:

Integrins in Hypertensive Remodeling

Ed VanBavel and Michael J. Mulvany
Hypertension 2006 47: 147-148. [Extract] [Full Text] [PDF]

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