心肌梗死后来源于心外膜脂肪组织的补体因子 D 通过介导 PARP-1 活性参与心肌细胞凋亡。
Complement factor D derived from epicardial adipose tissue participates in cardiomyocyte apoptosis after myocardial infarction by mediating PARP-1 activity.
机构信息
Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
出版信息
Cell Signal. 2023 Jan;101:110518. doi: 10.1016/j.cellsig.2022.110518. Epub 2022 Nov 6.
BACKGROUND
Acute myocardial infarction (MI) is considered to be the main cause of congestive heart failure. The aim of this study was to provide an in-depth analysis of athophysiological processes and provide key targets for intervention in the occurrence of acute MI.
METHODS
A rat model of MI was established by ligation of left anterior descending branch. Heart tissue, epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) were collected. H9c2 cells were used to explore the mechanism of complement factor D (CFD) regulating cardiomyocyte apoptosis.
RESULTS
Myocardial apoptosis were observed in MI rat, and more EAT was found in the MI group in vivo. The conditioned medium prepared by EAT (EAT-CM) significantly reduced the activity of H9c2 cells. The content of CFD in EAT was significantly increased, and CFD promoted cardiomyocyte apoptosis in vitro and CFD-IN1 (a selective inhibitor of CFD) could revised this effect. CFD induced poly ADP-ribosepolymerase-1 (PARP-1) overactivation. Furthermore, the addition of pan-caspase inhibitor Z-VAD in the SAT-CM + CFD group couldn't affect H9c2 cell apoptosis. CFD induced cell apoptosis via PARP-1 activation and PARP-1 inhibitor 3-Aminobenzamide could revise this effect. The injection of CFD-IN1 in MI rat model confirmed that inhibition of CFD activity alleviated cardiomyocytes apoptosis.
CONCLUSION
Our findings indicate that EAT mediating cardiomyocyte apoptosis after MI through secretion of CFD and activation of PARP-1 activity.
背景
急性心肌梗死（MI）被认为是充血性心力衰竭的主要原因。本研究旨在深入分析病理生理过程，并为急性 MI 发生时的干预提供关键靶点。
方法
结扎大鼠左前降支建立 MI 模型。收集心肌组织、心外膜脂肪组织（EAT）和皮下脂肪组织（SAT）。使用 H9c2 细胞探索补体因子 D（CFD）调节心肌细胞凋亡的机制。
结果
在 MI 大鼠中观察到心肌细胞凋亡，并且体内 MI 组中发现了更多的 EAT。EAT 制备的条件培养基（EAT-CM）显著降低了 H9c2 细胞的活性。EAT 中的 CFD 含量显著增加，CFD 在体外促进心肌细胞凋亡，而 CFD-IN1（CFD 的选择性抑制剂）可以修正这种作用。CFD 诱导多聚 ADP-核糖聚合酶-1（PARP-1）过度激活。此外，在 SAT-CM+CFD 组中添加泛半胱天冬酶抑制剂 Z-VAD 并不影响 H9c2 细胞凋亡。CFD 通过激活 PARP-1 诱导细胞凋亡，而 PARP-1 抑制剂 3-氨基苯甲酰胺可以修正这种作用。在 MI 大鼠模型中注射 CFD-IN1 证实抑制 CFD 活性可减轻心肌细胞凋亡。
结论
我们的研究结果表明，EAT 通过分泌 CFD 和激活 PARP-1 活性介导 MI 后心肌细胞凋亡。
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