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Cellular signalling

Cellular signalling

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Complement factor D derived from epicardial adipose tissue participates in cardiomyocyte apoptosis after myocardial infarction by mediating PARP-1 activity.

Published:1 January 2023 DOI: 10.1016/j.cellsig.2022.110518 PMID: 36351508
Shuang Hao, Jingchao Zhang, Yu Pei, Longhui Guo, Zhenxing Liang

Abstract

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.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
ComplementfactorD-IN-1 1386455-76-0 C21H19BrN6O3 18 suppliers Inquiry
ComplementfactorD-IN-1 1386455-76-0 C21H19BrN6O3 18 suppliers Inquiry
ComplementfactorD-IN-1 1386455-76-0 C21H19BrN6O3 18 suppliers Inquiry
ComplementfactorD-IN-1 1386455-76-0 C21H19BrN6O3 18 suppliers Inquiry

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