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Differential regulation of matrix metalloproteinases associated with aging and hypertension in the rat heart.
Robert, V; Besse, S; Sabri, A; Silvestre, J S; Assayag, P; Nguyen, V T; Swynghedauw, B; Delcayre, C.
Afiliación
  • Robert V; Institut National de la Sante et de la Recherche Medicale U127, Hôpital Lariboisiere, Paris, France.
Lab Invest ; 76(5): 729-38, 1997 May.
Article en En | MEDLINE | ID: mdl-9166291
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.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Metaloendopeptidasas / Hipertensión / Miocardio Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 1997 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Envejecimiento / Metaloendopeptidasas / Hipertensión / Miocardio Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: Lab Invest Año: 1997 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos