Matrix gene expression and decompensated heart failure: The aged SHR model

Impaired functional performance despite hypertrophic enlargement, and an ex cessive accumulation of extracellular matrix, are hallmarks of the decompen sated failing heart. Age is the leading risk factor for heart failure, and there is evidence suggesting that a number of age-associated changes in the cardiac phenotype predispose the heart to failure. The spontaneously hyper tensive rat (SHR) exhibits compensated cardiac hypertrophy followed by a tr ansition to heart failure in the last quartile of the lifespan, and thus pr ovides a useful model of the transition from stable compensated hypertrophy to decompensated heart failure in the context of aging. The transition to failure in the SHR is accompanied by marked changes in the expression of an array of genes in the heart, including increased expression of a number of genes associated with the extracellular matrix. Drug treatments that preve nt or reverse matrix gene expression in the SHR heart improve myocardial fu nction and survival. The aged SHR model of decompensated heart failure has provided insight into the role of the extracellular matrix in the transitio n to failure, and can be useful to further investigate the mechanistic base s of heart failure, as well as to evaluate the potential efficacy of novel therapeutic approaches to the treatment of heart failure. (C) 2000 Publishe d by Elsevier Science B.V. All rights reserved.