Transgenic Expression of Matrix Metalloproteinase-1 Inhibits Myocardial Fibrosis and Prevents the Transition to Heart Failure in a Pressure Overload Mouse Model

Abstract

Hypertension induces dysfunctional matrix remodeling that results in the development of myocardial fibrosis. Myocardial fibrosis adversely affects compliance, electrical activity and cardiac function in patients with hypertensive heart disease. Matrix metalloproteinases (MMPs) are a class of enzymes that regulate the remodeling of the matrix in response to pressure overload. Several studies have shown that the MMP-1/TIMP (tissue inhibitor of matrix metalloproteinase) ratio is decreased in hypertensive heart disease. However, the exact role that MMP-1 has in modulating the fibrotic response to hypertension is largely unknown. We hypothesized that cardiac expression of MMP-1 in mice would protect against the development of dysfunctional matrix remodeling during pressure overload. To investigate this, a suprarenal aortic banding model was utilized. Banded and unbanded MMP-1 transgenic mice were compared with appropriately matched wild-type mice. The banded mice were examined at 2 and 5 weeks after banding. MMP-1 attenuated the development of cardiac fibrosis, prevented left ventricular dilation and preserved cardiac function in mice that were exposed to pressure overload. Thus, MMP-1 protected the heart from the dysfunctional remodeling that occurs in response to chronic hypertension. In conclusion, these results suggest that strategies aimed at improving the MMP-1/TIMP balance in the myocardium may help to prevent the onset and progression of hypertensive heart disease.

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Correspondence to Jeanine M D'armiento.

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Foronjy, R., Sun, J., Lemaitre, V. et al. Transgenic Expression of Matrix Metalloproteinase-1 Inhibits Myocardial Fibrosis and Prevents the Transition to Heart Failure in a Pressure Overload Mouse Model. Hypertens Res 31, 725–735 (2008). https://doi.org/10.1291/hypres.31.725

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Keywords

  • hypertension
  • collagen
  • matrix metalloproteinase
  • fibrosis

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