alphaV integrins are necessary for eutrophic inward remodeling of small arteries in hypertension.
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 alpha and 3 beta integrins were identified and levels of expression investigated using RT-PCR. As pressure increased and remodeling advanced, integrin expression profiles revealed that only alphaV was significantly raised. In conjunction, we confirmed elevated integrin alphaV protein levels in TGR(mRen2)27 rat arteries and localization to the media using immunofluorescence. beta1 and beta3, but not beta5 integrin subunits were coprecipitated with integrin alphaV and are implicated in the eutrophic remodeling process. Administration of a peptide antagonist of alphaVbeta3 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 alphaV subunit of integrin alphaVbeta3, has a crucial role in the hypertensive remodeling process of TGR(mRen2)27 rat resistance arteries. During hypertensive remodeling, functions of specific alphaVbeta3-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.
Heerkens
Egidius H J
EH
Department of Medicine, University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom.
Shaw
Linda
L
Ryding
Alisdair
A
Brooker
Gillian
G
Mullins
John J
JJ
Austin
Clare
C
Ohanian
Vasken
V
Heagerty
Anthony M
AM
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics; D001794:Blood Pressure; D005455:Fluorescent Antibody Technique; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D047468:Immunoprecipitation; D039564:Integrin alphaV / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D016023:Integrins / Q000378:metabolism; D008638:Mesenteric Arteries / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics; D014018:Tissue Distribution; D017540:Tunica Media / Q000378:metabolism; D014655:Vascular Resistance
D039564:Integrin alphaV; D039302:Integrin alphaVbeta3; D016023:Integrins; C473112:Ren2 protein, mouse; D012083:Renin