Severe left ventricular hypertrophy with compensation masks cellular and subcellular Ca2+ defects, including a 68% decrease in SERCA2a and 35% decrease in RyR2, that limit contractile reserve.
Severe but compensated left ventricular hypertrophy masks underlying cellular and subcellular calcium handling defects that likely contribute to limited contractile reserve.
In conscious dogs with severe left ventricular (LV) hypertrophy (H) (doubling of LV/body weight), which developed gradually over 1 to 2 years after aortic banding, baseline LV function was well compensated. The LV was able to generate twice the LV systolic pressure without an increase in LV end-diastolic pressure, or decrease in LV dP/dt or LV wall thickening. However, LV myocytes isolated from LVH dogs exhibited impaired contraction at baseline and in response to Ca2+. There was no change in L-type Ca2+ channel current (ICa) density but the ability of ICa to trigger Ca2+ release from the sarcoplasmic reticulum (SR) was reduced. Immunoblot analysis revealed a 68% decrease in SERCA2a, and a 35% decrease in the number of ryanodine receptors (RyR2), with no changes in protein level of calsequestrin, Na+/Ca2+ exchanger or phospholamban (PLB), but with both RyR2 and PLB hyperphosphorylated. Spontaneous Ca2+ sparks in LVH cells were found to have prolonged duration but similar intensities despite the reduced SR Ca2+ load. A higher Ca2+ spark rate was observed in LVH cells, but this is inconsistent with the reduced SR Ca2+ content. However, Ca2+ waves were found to be less frequent, slower and were more likely to be aborted in Ca2+-challenged LVH cells. These paradoxical observations could be accounted for by a nonuniform SR Ca2+ distribution, RyR2 hyperphosphorylation in the presence of decreased global SR Ca2+ load. We conclude that severe LVH with compensation masks cellular and subcellular Ca2+ defects that remain likely contributors to the limited contractile reserve of LVH.
Song et al. (Fri,) conducted a other in Severe left ventricular hypertrophy. Severe left ventricular hypertrophy (induced by aortic banding) vs. Normal/baseline state was evaluated on Cellular and subcellular Ca2+ signaling and contractile function. Severe left ventricular hypertrophy with compensation masks cellular and subcellular Ca2+ defects, including a 68% decrease in SERCA2a and 35% decrease in RyR2, that limit contractile reserve.
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