| First Author | Yuasa D | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 3 | Pages | 1065-75 |
| PubMed ID | 26578687 | Mgi Jnum | J:230906 |
| Mgi Id | MGI:5766437 | Doi | 10.1096/fj.15-279885 |
| Citation | Yuasa D, et al. (2016) C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart. FASEB J 30(3):1065-75 |
| abstractText | Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.-Yuasa, D., Ohashi, K., Shibata, R., Mizutani, N., Kataoka, Y., Kambara, T., Uemura, Y., Matsuo, K., Kanemura, N., Hayakawa, S., Hiramatsu-Ito, M., Ito, M., Ogawa, H., Murate, T., Murohara, T., Ouchi, N. C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart. |
