Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in XXXX .

@entity455 @entity296 @entity6 @entity13088 @entity19 @entity409 @entity3839 @entity14571 @entity164 @entity460
@entity13088 is characterized by reduced cardiac contractility due to direct changes in heart muscle function independent of @entity455 . An important contributor to @entity409 in the @entity6 state is an impaired sarcoplasmic reticulum (SR) function, leading to disturbed intracellular @entity460 handling. We investigated whether overexpression of the SR @entity460 pump ( @entity14571 ) in @entity19 could reduce the impact of @entity6 on the development of @entity296 . @entity6 was induced by @entity3839 injection (200 mg/kg), and left ventricular (LV) function was analyzed in isolated hearts 3 weeks later. In @entity6 hearts systolic LV pressure was decreased by 15% and maximum speed of relaxation (-dP/dt) by 34%. Functional changes were also assessed in isolated papillary muscles. Active force was reduced by 61% and maximum speed of relaxation by 65% in the @entity6 state. The contractile impairment was accompanied by a 30% decrease in @entity14571 protein in @entity6 @entity19 . We investigated whether increased @entity14571 expression in transgenic @entity14571 -overexpressing @entity19 could compensate for the @entity6 -induced decrease in cardiac function. Under normal conditions, @entity14571 overexpressors show improved contractile performance relative to @entity164 ( @entity164 ) @entity19 (-dP/dt: 3,169 vs. 2,559 mmHg/s, respectively). Measurement of LV function in hearts from @entity6 @entity14571 @entity19 revealed systolic and diastolic functions that were similar to @entity164 control @entity19 and markedly improved relative to @entity6 @entity164 @entity19 (-dP/dt: 2,534 vs. 1,690 mmHg/s in @entity6 @entity14571 vs. @entity6 @entity164 @entity19 , respectively). Similarly, the contractile behavior of isolated papillary muscles from @entity6 @entity14571 @entity19 was not different from that of control @entity19 . @entity14571 protein expression was higher (60%) in @entity6 @entity14571 @entity19 than @entity164 @entity6 @entity19 . These results indicate that overexpression of @entity14571 can protect @entity6 hearts from severe @entity409 , presumably by improving the @entity460 sequestration of the SR.
