Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction.
Adipolin/C1q/Tnf-related protein 12 prevents adverse cardiac remodeling after myocardial infarction.
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DOI：
10.1371/journal.pone.0243483
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Ouchi N
中科院分区：
文献类型：
--
作者：
Takikawa T;Ohashi K;Ogawa H;Otaka N;Kawanishi H;Fang L;Ozaki Y;Eguchi S;Tatsumi M;Takefuji M;Murohara T;Ouchi N
心肌梗死（MI）是全球范围内的主要死亡原因。我们以前确定adipolin，也被称为C1 q/TNF相关蛋白12，作为一种抗炎脂肪因子，具有保护功能，对代谢和血管疾病。在这里，我们研究了脂蛋白对心肌梗死小鼠模型心肌重塑的影响。对雄性脂蛋白敲除（APL-KO）和野生型（WT）小鼠进行左前降支冠状动脉的永久结扎以产生MI。与WT小鼠相比，APL-KO小鼠在MI后表现出心脏重量/体重和肺重量/体重的比率增加。与WT小鼠相比，APL-KO小鼠MI后左心室舒张期内径增加，缩短分数降低。与WT小鼠相比，APL-KO小鼠在MI后心脏中表现出促炎介质表达增加和心肌细胞凋亡增强。MI手术后，WT小鼠全身给予表达adipolin的腺病毒载体可改善左心室收缩功能障碍，并降低心脏促炎基因的表达。用adipolin蛋白处理培养的心肌细胞可减少脂多糖诱导的促炎介质表达和缺氧诱导的细胞凋亡。adipolin蛋白处理增加心肌细胞Akt磷酸化。抑制PI 3激酶/Akt信号转导可逆转adipolin在心肌细胞中的抗炎和抗凋亡作用。我们的数据表明，adipolin改善心肌梗死后的心肌病理性重构，至少部分是通过其减少心肌炎症反应和细胞凋亡的能力。
Myocardial infarction (MI) is a leading cause of death worldwide. We previously identified adipolin, also known as C1q/Tnf-related protein 12, as an anti-inflammatory adipokine with protective features against metabolic and vascular disorders. Here, we investigated the effect of adipolin on myocardial remodeling in a mouse model of MI. Male adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to the permanent ligation of the left anterior descending coronary artery to create MI. APL-KO mice exhibited increased ratios of heart weight/body weight and lung weight/body weight after MI compared with WT mice. APL-KO mice showed increased left ventricular diastolic diameter and decreased fractional shortening after MI compared with WT mice. APL-KO mice exhibited increased expression of pro-inflammatory mediators and enhanced cardiomyocyte apoptosis in the post-MI hearts compared with WT mice. Systemic administration of adenoviral vectors expressing adipolin to WT mice after MI surgery improved left ventricular contractile dysfunction and reduced cardiac expression of pro-inflammatory genes. Treatment of cultured cardiomyocytes with adipolin protein reduced lipopolysaccharide-induced expression of pro-inflammatory mediators and hypoxia-induced apoptosis. Treatment with adipolin protein increased Akt phosphorylation in cardiomyocytes. Inhibition of PI3 kinase/Akt signaling reversed the anti-inflammatory and anti-apoptotic effects of adipolin in cardiomyocytes. Our data indicate that adipolin ameliorates pathological remodeling of myocardium after MI, at least in part, by its ability to reduce myocardial inflammatory response and apoptosis.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Enomoto T;Ohashi K;Shibata R;Kambara T;Uemura Y;Yuasa D;Kataoka Y;Miyabe M;Matsuo K;Joki Y;Hayakawa S;Hiramatsu-Ito M;Ito M;Murohara T;Ouchi N
通讯作者：
Ouchi N
影响因子：
7.7
作者：
Bell-Anderson KS;Funnell AP;Williams H;Mat Jusoh H;Scully T;Lim WF;Burdach JG;Mak KS;Knights AJ;Hoy AJ;Nicholas HR;Sainsbury A;Turner N;Pearson RC;Crossley M
通讯作者：
Crossley M
影响因子：
3.8
作者：
Fadaei, Reza;Moradi, Nariman;Fallah, Soudabeh
通讯作者：
Fallah, Soudabeh
影响因子：
24
作者：
Gonzalez, Arantxa;Ravassa, Susana;Diez, Javier
通讯作者：
Diez, Javier