Abstract P356: Mmp-2/timp-2 Imbalance and Increased Collagen Production are Crucial to the Transition From Compensated Cardiac Hypertrophy to Heart Failure in Rats Subjected to Abdominal Aorta Constriction

Abstract

Background: Hypertension causes cardiac hypertrophy, cardiac dysfunction, and heart failure (HF). The role of matrix metalloproteinases (MMPs) in the cardiac remodeling induced by hypertension has been demonstrated. Our objective was to evaluate whether temporal changes during the transition from compensated cardiac hypertrophy to HF may be dependent of MMP-2 activity in a model of pressure overload cardiac hypertrophy. Methods: Male Wistar rats were subjected to abdominal aorta constriction and observed after 30, 60, 90 days post surgery (dps). Systolic and diastolic cardiac functions were analyzed. Picrosirius red staining was used to quantify interstitial collagen in the left ventricle. Western blotting was performed for MMP-2 and tissue inhibitor of matrix metalloproteinase (TIMP)-2. Data were considered significant when p<0.05. Results: At 90 dps, 70% (28 of 40) presented hypertrophic hearts (HH) and 30% (12 of 40) hypertrophic+dilated hearts (HD). The ejection fraction (EF) and fractional shortening (FS) at 30, 60 and 90 dps in the HH group were not different from sham. In the HD group, a decrease of 45% in the EF (35.46±3.29%) and 41.5% in the FS (21.60±5.34%) was observed compared to sham (62.62±5.82%; 35.28±2.47%, respectively). In relation to diastolic parameters, the mitral E-wave velocity increased 47% (1279±127) and E/E’ ratio increased 60% (68.14±16.78) only in the HD group in relation to sham (866±134; 26.99±5.47, respectively). Increased interstitial collagen was observed at 30 (2.08±0.14%), 60 (2.48±0.29%) and 90 dps in the HH (2.83±0.18%) and HD groups (2.82±0.16%) when compared to sham (1.62±0.15%). There is no alteration in the MMP-2 expression at 30 and 60 dps. An increase of 54.4% in the HH group (1.22±0.23) and 51% in the HD (1.19±0.34) was observed in relation to sham (0.79±0.32). TIMP-2 expression increased 82% at 60 dps (1.30±0.17), 62% in the HH group (1.15±0.31) and 51% in the HD group (1.07±0.31) when compared to sham (0.71±1.12). Conclusion: The imbalance between MMP-2 and TIMP-2 expression associated with increased collagen content suggests that the deregulation of MMP-2 expression by TIMP-2 could contribute to the transition from compensated cardiac hypertrophy to heart failure.