| First Author | Talukder MA | Year | 2008 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 294 |
| Issue | 3 | Pages | H1426-34 |
| PubMed ID | 18203847 | Mgi Jnum | J:132620 |
| Mgi Id | MGI:3776366 | Doi | 10.1152/ajpheart.01016.2007 |
| Citation | Talukder MA, et al. (2008) Is reduced SERCA2a expression detrimental or beneficial to postischemic cardiac function and injury? Evidence from heterozygous SERCA2a knockout mice. Am J Physiol Heart Circ Physiol 294(3):H1426-34 |
| abstractText | Recent studies have demonstrated that increased expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) 2a improves myocardial contractility and Ca(2+) handling at baseline and in disease conditions, including myocardial ischemia-reperfusion (I/R). Conversely, it has also been reported that pharmacological inhibition of SERCA might improve postischemic function in stunned hearts or in isolated myocardium following I/R. The goal of this study was to test how decreases in SERCA pump level/activity affect cardiac function following I/R. To address this question, we used a heterozygous SERCA2a knockout (SERCA2a(+/-)) mouse model with decreased SERCA pump levels and studied the effect of myocardial stunning (20-min ischemia followed by reperfusion) and infarction (30-min ischemia followed by reperfusion) following 60-min reperfusion. Our results demonstrate that postischemic myocardial relaxation was significantly impaired in SERCA2a(+/-) hearts with both stunning and infarction protocols. Interestingly, postischemic recovery of contractile function was comparable in SERCA2a(+/-) and wild-type hearts subjected to stunning. In contrast, following 30-min ischemia, postischemic contractile function was reduced in SERCA2a(+/-) hearts with significantly larger infarction. Rhod-2 spectrofluorometry revealed significantly higher diastolic intracellular Ca(2+) in SERCA2a(+/-) hearts compared with wild-type hearts. Both at 30-min ischemia and 2-min reperfusion, intracellular Ca(2+) levels were significantly higher in SERCA2a(+/-) hearts. Electron paramagnetic resonance spin trapping showed a similar extent of postischemic free-radical generation in both strains. These data provide direct evidence that functional SERCA2a level, independent of oxidative stress, is crucial for postischemic myocardial function and salvage during I/R. |
