| First Author | Gao C | Year | 2015 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 308 |
| Issue | 12 | Pages | H1583-91 |
| PubMed ID | 25888509 | Mgi Jnum | J:224635 |
| Mgi Id | MGI:5688446 | Doi | 10.1152/ajpheart.00346.2014 |
| Citation | Gao C, et al. (2015) TNF-alpha antagonism ameliorates myocardial ischemia-reperfusion injury in mice by upregulating adiponectin. Am J Physiol Heart Circ Physiol 308(12):H1583-91 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) antagonism alleviates myocardial ischemia-reperfusion (MI/R) injury. However, the mechanisms by which the downstream mediators of TNF-alpha change after acute antagonism during MI/R remain unclear. Adiponectin (APN) exerts anti-ischemic effects, but it is downregulated during MI/R. This study was conducted to investigate whether TNF-alpha is responsible for the decrease of APN, and whether antagonizing TNF-alpha affects MI/R injury by increasing APN. Male adult wild-type (WT), APN knockout (APN KO) mice, and those with cardiac knockdowns of APN receptors via siRNA injection were subjected to 30 min of MI followed by reperfusion. The TNF-alpha antagonist etanercept or globular domain of APN (gAD) was injected 10 min before reperfusion. Etanercept ameliorated MI/R injury in WT mice as evidenced by improved cardiac function, and reduced infarct size and cardiomyocyte apoptosis. APN concentrations were augmented in response to etanercept, followed by an increase in AMP-activated protein kinase phosphorylation. Etanercept still increased cardiac function and reduced infarct size and apoptosis in both APN KO and APN receptors knockdown mice. However, its potential was significantly weakened in these mice compared with the WT mice. TNF-alpha is responsible for the decrease in APN during MI/R. The cardioprotective effects of TNF-alpha neutralization are partially due to the upregulation of APN. The results provide more insight into the TNF-alpha-mediated signaling effects during MI/R and support the need for clinical trials to validate the efficacy of acute TNF-alpha antagonism in the treatment of MI/R injury. |
