Compensated hypertrophy of cardiac ventricles in aged transgenic FVB/N mice overexpressing calsequestrin.

Abstract

Cardiac-specific overexpression of murine cardiac calsequestrin results in depressed contractile parameters and hypertrophy in transgenic mice. To determine the long-term consequences of calsequestrin overexpression, the cardiac phenotype of young (2-3-months old) and aged (17 months old) transgenic FVB/N mice was characterized. Ventricular/body weight ratios, which were increased in young transgenics compared with wild-types, were unaltered with age. Left atria of aged transgenics exhibited enlargement and mineralization, but their ventricles did not display fibrosis, mineralization and other injuries. Although echocardiography suggested a time-dependent change in ventricular geometry and loading conditions in vivo, as well as an age-dependent reduction of left ventricular fractional shortening in transgenic mice, Langendorff-perfused hearts of young and aged transgenics indicated that there were no age-related reductions of contractile parameters (+/-dP/dt). Furthermore, neither genotype nor age altered lung/body weight ratios. Thus, our findings suggest that left ventricular performance in calsequestrin overexpressing mice becomes apparently depressed with age, but this depression is not associated with progressive reduction of left ventricular contractility and heart failure.