Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 284; no. 1; pp. H364 - H371
• Main Authors: Creemers, Esther E. J. M, Davis, Jeniffer N, Parkhurst, Andrea M, Leenders, Peter, Dowdy, Kathryn B, Hapke, Elizabeth, Hauet, Anne M, Escobar, Patricia G, Cleutjens, Jack P. M, Smits, Jos F. M, Daemen, Mat J. A. P, Zile, Michael R, Spinale, Francis G
• Format: Journal Article
• Language: English
• Published: United States 01.01.2003
• Subjects: Animals; Echocardiography; Mice; Mice, Knockout - genetics; Myocardial Infarction - physiopathology; Space life sciences; Tissue Inhibitor of Metalloproteinase-1 - deficiency; Tissue Inhibitor of Metalloproteinase-1 - genetics; Ventricular Function, Left; Ventricular Remodeling - physiology; Non-programmatic
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00511.2002

Departments of 1  Pathology and 3  Pharmacology, Cardiovascular Research Institute Maastricht, University of Maastricht, 6200 MD Maastricht, The Netherlands; and Departments of 2  Cardiothoracic Surgery and 4  Cardiology, Medical University of South Carolina, Charleston, South Carolina 29425 Recent studies have been directed at modulating the heart failure process through inhibition of activated matrix metalloproteinases (MMPs). We hypothesized that a loss of MMP inhibitory control by tissue inhibitor of MMP (TIMP)-1 deficiency alters the course of postinfarction chamber remodeling and induced chronic myocardial infarction (MI) in wild-type (WT) and TIMP-1 / mice. Left ventricular (LV) pressure-volume loops obtained from WT and TIMP-1 / mice demonstrated that LV end-diastolic volume [52 ± 4 (WT) vs. 71 ± 6 (TIMP-1 / ) µl] and LV end-diastolic pressure [9.0 ± 1.2 (WT) vs. 12.7 ±   1.4 (TIMP-1 / ) mmHg] were significantly increased in the TIMP-1 / mice 2 wk after MI. LV contractility was reduced to a similar degree in the WT and TIMP-1 / groups after MI, as indicated by a significant fall in the LV end-systolic pressure-volume relationship. Ventricular weight and cross-sectional areas of LV myocytes were significantly increased in TIMP-1 / mice, indicating that the hypertrophic response was more pronounced. The observed significant loss of fibrillar collagen in the TIMP-1 / controls may have been an important contributory factor for the observed LV alterations in the TIMP-1 / mice after MI. These findings demonstrate that TIMP-1 deficiency amplifies adverse LV remodeling after MI in mice and emphasizes the importance of local endogenous control of cardiac MMP activity by TIMP-1. myocardial remodeling; pressure-volume loops