CTRP3 protected against doxorubicin-induced cardiac dysfunction, inflammation and cell death via activation of Sirt1.

Abstract

BACKGROUND:

Inflammation and myocytes apoptosis play critical roles in the development of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found that C1q/tumour necrosis factor-related protein-3 (CTRP3) could inhibit cardiac inflammation and apoptosis of myocytes but its role in DOX-induced heart injury remains largely unknown. Our study aimed to investigate whether CTRP3 protected against DOX-induced heart injury and the underlying mechanism.

METHODS:

We overexpressed CTRP3 in the hearts using an adeno-associated virus system. The mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to induce short-term model for cardiomyopathy. The morphological examination and biochemical analysis were used to evaluate the effects of CTRP3. H9C2 cells were used to verify the protective role of CTRP3 in vitro.

RESULTS:

Myocardial CTRP3 protein levels were reduced in DOX-treated mice. Cardiac specific-overexpression of CTRP3 preserved heart dysfunction, and attenuated cardiac inflammation and cell loss induced by DOX in vivo and in vitro. CTRP3 could activate silent information regulator 1 (Sirt1) in vivo and in vitro. Moreover, specific inhibitor of Sirt1 and the silence of Sirt1 could abolish the protective effects of CTRP3 against DOX-induced inflammation and apoptosis.

CONCLUSION:

CTRP3 protected against DOX-induced heart injury via activation of Sirt1. CTRP3 has therapeutic potential for the treatment of DOX cardiotoxicity.

• Authors: Yu-Pei Yuan, Zhen-Guo Ma, Xin Zhang, Si-Chi Xu, Xiao-Feng Zeng, Zheng Yang, Wei Deng, Qi-Zhu Tang
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 114 Pg. 38-47 (01 2018) ISSN: 1095-8584 [Electronic] England
• PMID: 29061338 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Adipokines
• CORS26 protein, mouse
• Cardiotonic Agents
• Doxorubicin
• Sirtuin 1

Topics

• Adipokines (metabolism)
• Animals
• Cardiotonic Agents (metabolism)
• Cell Death
• Doxorubicin (adverse effects)
• Heart (physiopathology)
• Inflammation (pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Sirtuin 1 (metabolism)