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首页> 外文期刊>Molecular and Cellular Biology >C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism
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C1q/Tumor Necrosis Factor-Related Protein 9 Protects against Acute Myocardial Injury through an Adiponectin Receptor I-AMPK-Dependent Mechanism

机译：C1q /肿瘤坏死因子相关蛋白9通过脂联素受体I-AMPK依赖性机制保护免受急性心肌损伤。

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Obesity is a risk factor for cardiovascular disease. C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adipokine that is downregulated by obesity. We investigated the role of CTRP9 in cardiac injury with loss-of-function genetic manipulations and defined the receptor-mediated signaling pathway downstream of this adipokine. CTRP9-knockout (CTRP9-KO) mice at the age of 12 weeks were indistinguishable from wild-type (WT) mice under basal conditions. CTRP9-KO mice had exacerbated contractile left ventricle dysfunction following intraperitoneal injection of lipopolysaccharide (LPS) compared to WT mice. Administration of LPS to CTRP9-KO mice also resulted in increased expression of proinflammatory cytokines and oxidative stress markers in the heart compared to WT mice. Likewise, CTRP9-KO mice showed increased myocardial infarct size and elevated expression of inflammatory mediators in ischemic heart following ischemia and reperfusion compared to WT mice. Treatment of cardiac myocytes with CTRP9 protein led to suppression of LPS-induced expression of proinflammatory genes, which was reversed by blockade of AMPK or ablation of adiponectin receptor I (AdipoR1). Systemic delivery of CTRP9 attenuated LPS-induced cardiac dysfunction in WT mice but not in muscle-specific transgenic mice expressing dominant-negative mutant form of AMPK or in AdipoR1-knockout mice. CTRP9 protects against acute cardiac damage in response to pathological stimuli by suppressing inflammatory reactions through AdipoR1/AMPK-dependent mechanisms.
机译：肥胖是心血管疾病的危险因素。 C1q /肿瘤坏死因子相关蛋白9（CTRP9）是由于肥胖而下调的脂肪因子。我们用功能丧失的基因操作方法研究了CTRP9在心脏损伤中的作用，并确定了该脂肪因子下游的受体介导的信号通路。在基础条件下，在12周龄时CTRP9敲除（CTRP9-KO）小鼠与野生型（WT）小鼠没有区别。与野生型小鼠相比，腹膜内注射脂多糖（LPS）后，CTRP9-KO小鼠加剧了收缩性左心室功能障碍。与WT小鼠相比，向CTRP9-KO小鼠施用LPS还导致心脏中促炎性细胞因子和氧化应激标志物的表达增加。同样，与WT小鼠相比，CTRP9-KO小鼠在缺血和再灌注后的缺血性心脏中显示出心肌梗塞面积增加和炎症介质表达升高。用CTRP9蛋白处理心肌细胞可导致LPS诱导的促炎基因表达受到抑制，这可通过阻断AMPK或切除脂联素受体I（AdipoR1）来逆转。 CTRP9的系统性传递可减轻WT小鼠中LPS诱导的心脏功能障碍，但不能表达AMPK显性负突变形式的肌肉特异性转基因小鼠或AdipoR1基因敲除小鼠。 CTRP9通过抑制AdipoR1 / AMPK依赖性机制引起的炎症反应，保护其免受病理性刺激引起的急性心脏损害。

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