Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2 dependent mechanisms
Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2 dependent mechanisms
复制标题
DOI：
10.1038/nm1295
复制
发表时间：
2005-10-01
期刊：
影响因子：
82.9
通讯作者：
Walsh, K
中科院分区：
文献类型：
--
作者：
Shibata, R;Sato, K;Walsh, K
肥胖相关的疾病与缺血性心脏病的发展有关。脂联素是一种循环脂肪衍生的细胞因子，在肥胖者和心肌梗死后表达下调。在这里，我们研究脂联素在急性损伤后心肌重塑中的作用。脂联素缺陷型(APN-KO)小鼠与野生型小鼠相比，心肌缺血再灌注后心肌梗死面积增加，心肌细胞凋亡和肿瘤坏死因子-α表达增加。脂联素的应用减少了APN-KO和野生型小鼠的梗塞面积、细胞凋亡和肿瘤坏死因子-α的产生。在培养的心肌细胞中，脂联素抑制细胞凋亡和肿瘤坏死因子-α的产生。显性负性AMP激活蛋白激酶(AMPK)可逆转脂联素对细胞凋亡的抑制作用，但不影响脂联素对肿瘤坏死因子-α产生的抑制作用。脂联素诱导心肌细胞环氧合酶(COX)-2依赖的前列腺素E-2的合成，COX-2的抑制逆转了脂联素对肿瘤坏死因子-α的产生和心肌梗死面积的抑制作用。这些数据表明，脂联素通过AMPK和COX-2两种依赖机制来保护心脏免受缺血再灌注损伤。
Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wildtype mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase ( AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E-2 in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.