Structural remodelling in heart failure: gelatinase induction.
OBJECTIVE: Rapid ventricular pacing in the dog produces severe congestive cardiac failure in association with neurohumoral activation and marked depression of cardiac function. This syndrome is associated with left ventricular dilation, significant wall thinning, assumption of a more globular shape and disruption of the cardiac collagen infrastructure, given that the fibrillar collagen network is a major determinant of cardiac architecture. The purpose of the present study was to investigate whether there was evidence of increased activity of matrix metalloproteinases. The authors speculated that it could play an important permissive role in myocyte realignment, thereby resulting in the changes in cardiac size and shape. DESIGN: Twenty-one male mongrel dogs underwent ventricular pacing and were allocated into one of three groups: early heart failure (n = 6), severe heart failure (n = 7) and recovered heart failure (n = 8). Measurements included echocardiographic and hemodynamic parameters, plasma noradrenaline levels, left ventricular noradrenaline levels and matrix metalloproteinase activity. RESULTS: The study showed gelatinase activity present in normal left ventricular tissue predominantly attributable to a 72 kDa gelatinase (85%) and, to a much lesser extent, by a 92 kDa gelatinase (15%). Levels of 92 kDa gelatinase increased slightly within one week and reached maximal levels with severe heart failure, where it represented over one-half of the total gelatinase activity. In animals allowed to recover for four weeks, 92 kDa gelatinase decreased significantly to approximately 50% of the levels observed at severe heart failure. The levels of 72 kDa gelatinase did not change significantly during any experimental condition. Significant correlations between 92 kDa percentage activity and systolic and diastolic left ventricular areas across all time-points were evident (r = 0.59 and 0.63, respectively, P < 0.05 for both). CONCLUSION: The association of 92 kDa gelatinase with changes in left ventricular area suggests a possible modulating role for this matrix metalloproteinase in disruption of the fibrillar components of the left ventricular extracellular matrix.
Armstrong, PW; Moe, GW; Howard, RJ; Grima, EA; Cruz, TF
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