Ablation of phospholamban and sarcolipin results in cardiac hypertrophy and decreased cardiac contractility

作者：Shanmugam Mayilvahanan; Gao Shumin; Hong Chull; Fefelova Nadezhda; Nowycky Martha C; Xie Lai Hua; Periasamy Muthu; Babu Gopal J^*

来源：Cardiovascular Research, 2011, 89(2): 353-361.

DOI：10.1093/cvr/cvq294

• SERCA
• Phospholamban
• Sarcolipin
• Double knockout
• Calcium
• Calcium transient
• Aortic banding
• Cardiac function

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.

• 出版日期2011-2