Key result
Constitutive activation of the SERCA pump via ablation of phospholamban and sarcolipin resulted in cardiac hypertrophy and worsened cardiac function upon ageing and pressure overload in mice.
Why the study?
Does constitutive activation of the SERCA pump via PLN and SLN ablation improve cardiac contractility in normal and pressure-overloaded mice?
Does constitutive activation of the SERCA pump via PLN and SLN ablation improve cardiac contractility in normal and pressure-overloaded mice?
Constitutive activation of the SERCA pump by ablating PLN and SLN is detrimental to cardiac function, emphasizing the need for dynamic regulation of SERCA.
AIMS: Improving the sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase (SERCA) function has clinical implications in treating heart failure. The present study aimed to determine the effect of constitutive activation of the SERCA pump on cardiac contractility in normal mice and during pressure-overload-induced cardiac hypertrophy. METHODS AND RESULTS: The SERCA pump was constitutively activated in both atrial and ventricular chambers of the mouse heart by ablating its key regulators, phospholamban (PLN) and sarcolipin (SLN). The double-knockout (dKO) mice for PLN and SLN showed increased SERCA pump activity, Ca(2+) transients and SR Ca(2+) load, and developed cardiac hypertrophy. Echocardiographic measurements showed that the basal cardiac function was not affected in the young dKO mice. However, the cardiac function worsened upon ageing and when subjected to pressure overload. CONCLUSION: Our studies suggest that the constitutive activation of the SERCA pump is detrimental to cardiac function. Our findings also emphasize the need for dynamic regulation of the SERCA pump by PLN and/or SLN to maintain cardiac contractility in normal conditions and during pathophysiological states.
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Shanmugam et al. (2010) studied Cardiac hypertrophy. Ablation of phospholamban (PLN) and sarcolipin (SLN) vs. Normal mice was evaluated on Cardiac contractility and hypertrophy. Constitutive activation of the SERCA pump via ablation of phospholamban and sarcolipin resulted in cardiac hypertrophy and worsened cardiac function upon ageing and pressure overload in mice.
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