@article{JTD24263,
author = {Shuai Li and Jian Ma and Jing-Bo Li and James C. Lacefield and Douglas L. Jones and Tian-Qing Peng and Meng Wei},
title = {Over-expression of calpastatin attenuates myocardial injury following myocardial infarction by inhibiting endoplasmic reticulum stress},
journal = {Journal of Thoracic Disease},
volume = {10},
number = {9},
year = {2018},
keywords = {},
abstract = {Background: Ischemic heart injury activates calpains and endoplasmic reticulum (ER) stress in cardiomyocytes. This study investigated whether over-expression of calpastatin, an endogenous calpain inhibitor, protects the heart against myocardial infarction (MI) by inhibiting ER stress.
Methods: Mice over-expressing calpastatin (Tg-CAST) and littermate wild type (WT) mice were divided into four groups: WT-sham, Tg-CAST-sham, WT-MI, and Tg-CAST-MI, respectively. WT-sham and Tg- CAST-sham mice showed similar cardiac function at baseline. MI for 7 days impaired cardiac function in WT-MI mice, which was ameliorated in Tg-CAST-MI mice.
Results: Tg-CAST-MI mice exhibited significantly decreased diameter of the left ventricular cavity, scar area, and cardiac cell death compared to WT-MI mice. WT-MI mice had higher cardiac expression of C/ EBP homologous protein (CHOP) and BIP, indicators of ER stress, compared to WT-sham mice, indicative of MI-induced ER stress. This increase was abolished in Tg-CAST-MI hearts. Furthermore, administration of tauroursodeoxycholic acid, an inhibitor of ER stress, reduced MI-induced expression of CHOP and BIP, scar area, and myocardial dysfunction. In an in vitro model of oxidative stress, H2O2 stimulation of H9c2 cardiomyoblasts induced calpain activation, CHOP expression, and cell death, all of which were prevented by the calpain inhibitor PD150606, as well as CHOP silencing.
Conclusions: Over-expression of calpastatin ameliorates MI-induced myocardial injury in mice. These protective effects of calpastatin are partially achieved through suppression of the ER stress/CHOP pathway.},
issn = {2077-6624}, url = {https://jtd.amegroups.org/article/view/24263}
}