title: Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.
abstract: Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events.
authors.affiliation: Program in Biomedical Sciences, Université de Montréal, Montréal, Québec, Canada; Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Tardif
authors.affiliation: Departement of Physiology, Université de Montréal, Montréal, Québec, Canada; and Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hertig
authors.affiliation: Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Natacha
authors.initials: N
authors.lastname: Duquette
authors.affiliation: Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Villeneuve
authors.affiliation: Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Ismail
authors.initials: I
authors.lastname: El-Hamamsy
authors.affiliation: Program in Biomedical Sciences, Université de Montréal, Montréal, Québec, Canada; Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanguay
authors.affiliation: Departement of Physiology, Université de Montréal, Montréal, Québec, Canada; and Research Center, Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada angelo.calderone@umontreal.ca.
authors.forename: Angelino
authors.initials: A
authors.lastname: Calderone
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004261:DNA Replication; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D066253:Vascular Remodeling
chemical_list: D064231:Nestin; D000804:Angiotensin II; D004815:Epidermal Growth Factor
keywords: aorta; carotid artery; hypertension; nestin; vascular remodeling