title: Differential regulation of matrix metalloproteinases associated with aging and hypertension in the rat heart.
abstract: We compared two models of cardiac fibrosis in which collagen synthesis is controlled at different levels. Regulation is pretranslational in aldosterone-salt-induced hypertension in young rats and posttranslational in 24-month-old rats. However, little is known about the role of matrix metalloproteinases (MMP) in fibrosis development. Ventricular MMP activities were studied by zymography, and MMP-2 and MMP-1 mRNA levels were determined using slot-blot and ribonuclease protection assay, respectively. After 1 month of aldosterone-salt treatment, proMMP-2, MMP-2, and proMMP-1 collagenolytic activities and their gene expression were unchanged compared with sham-operated rats. After 2 months, total MMP-2 activity was increased by 40% with parallel stimulation of its gene expression. These changes were localized by in situ zymography within the media of coronary vessels. These results suggest that MMP play a prominent role in vascular remodeling during the first steps of hypertension. During aging, however, there were 40% and 45% decreases in MMP-2 and proMMP-1 activity, respectively, with a corresponding down-regulation of MMP-2 mRNA. These observations suggest that depression of the degradative pathway is partly responsible for age-associated fibrosis. Thus, MMP have differing involvements in the cardiac remodeling associated with hypertension or aging.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale U127, Hôpital Lariboisiere, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Robert
authors.forename: S
authors.initials: S
authors.lastname: Besse
authors.forename: A
authors.initials: A
authors.lastname: Sabri
authors.forename: J S
authors.initials: JS
authors.lastname: Silvestre
authors.forename: P
authors.initials: P
authors.lastname: Assayag
authors.forename: V T
authors.initials: VT
authors.lastname: Nguyen
authors.forename: B
authors.initials: B
authors.lastname: Swynghedauw
authors.forename: C
authors.initials: C
authors.lastname: Delcayre
mesh_terms: D000375:Aging; D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004719:Endomyocardial Fibrosis / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D012333:RNA, Messenger; D003094:Collagen; D008666:Metalloendopeptidases