Does TIMP-1 deficiency exacerbate LV remodeling after myocardial infarction in mice?
TIMP-1 deficiency amplifies adverse LV remodeling after myocardial infarction in mice, highlighting the importance of endogenous control of cardiac MMP activity.
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(-/-)) microl 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.
Creemers et al. (Wed,) studied this question.