In dogs with severe experimental mitral regurgitation, the 23% increase in LV mass-to-body weight ratio at 3 months resulted primarily from a decrease in the rate of protein degradation.
In a canine model of mitral regurgitation, cardiac hypertrophy is primarily driven by a decrease in protein degradation rather than an increase in protein synthesis.
This study tested whether the modest hypertrophy that develops in dogs in response to mitral regurgitation is due to a relatively small change in the rate of protein synthesis or, alternatively, is due to a decreased rate of protein degradation. After 3 mo of severe experimental mitral regurgitation, the left ventricular (LV) mass-to-body weight ratio increased by 23% compared with baseline values. This increase in LV mass occurred with a small, but not statistically significant, increase in the fractional rate of myosin heavy chain (MHC) synthesis (Ks), as measured using continuous infusion with 3Hleucine in dogs at 2 wk, 4 wk, and 3 mo after creation of severe mitral regurgitation. Translational efficiency was unaffected by mitral regurgitation as measured by the distribution of MHC mRNA in polysome gradients. Furthermore, there was no detectable increase in translational capacity as measured by either total RNA content or the rate of ribosome formation. These data indicate that translational mechanisms that accelerate the rate of cardiac protein synthesis are not responsive to the stimulus of mitral regurgitation. Most of the growth after mitral regurgitation was accounted for by a decrease in the fractional rate of protein degradation, calculated by subtracting fractional rates of protein accumulation at each time point from the corresponding Ks values. We conclude that 1) volume overload produced by severe mitral regurgitation does not trigger substantial increases in the rate of protein synthesis and 2) the modest increase in LV mass results primarily from a decrease in the rate of protein degradation.
Matsuo et al. (Wed,) conducted a other in Cardiac hypertrophy secondary to mitral regurgitation. Severe experimental mitral regurgitation vs. Baseline values was evaluated on Left ventricular (LV) mass-to-body weight ratio. In dogs with severe experimental mitral regurgitation, the 23% increase in LV mass-to-body weight ratio at 3 months resulted primarily from a decrease in the rate of protein degradation.