Effect of PKC inhibitor on experimental autoimmune myocarditis in Lewis rats

Chunlian Zhong; Yang Wu; He Chang; Chunxiao Liu; Li Zhou; Jun Zou; Zhi Qi

doi:10.18632/oncotarget.17018

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Research Papers:

Effect of PKC inhibitor on experimental autoimmune myocarditis in Lewis rats

Chunlian Zhong, Yang Wu, He Chang, Chunxiao Liu, Li Zhou, Jun Zou and Zhi Qi _

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Oncotarget. 2017; 8:54187-54198. https://doi.org/10.18632/oncotarget.17018

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Abstract

Chunlian Zhong1, Yang Wu1,2, He Chang1,2, Chunxiao Liu1,2, Li Zhou1, Jun Zou1 and Zhi Qi1

1Department of Basic Medical Sciences, Medical College of Xiamen University, Xiang’an Nan Lu, Xiamen, China

2Xiamen Cardiovascular Hospital, Medical College of Xiamen University, Xiamen, China

Correspondence to:

Jun Zou, email: [email protected]

Zhi Qi, email: [email protected]

Keywords: myocarditis, PKC signaling, PKC inhibitor, apoptosis, inflammation

Abbreviations: EAM-experimental autoimmune myocarditis, ANP-atrial natriuretic peptide, BNP-brain natriuretic peptide

Received: January 02, 2017 Accepted: March 31, 2017 Published: April 10, 2017

ABSTRACT

Myocarditis is a major cause of sudden, unexpected death in young people. However, it is still one of the most challenging diseases to treat in cardiology. In the present study, we showed that both expression level and activity of PKC-α were up-regulated in the rat heart of experimental autoimmune myocarditis (EAM). Intraperitoneal administration of PKC inhibitor (Ro-32-0432) at the end of the most severe inflammation period of EAM still significantly reduced the EAM induced expression of failure biomarkers. Furthermore, Ro-32-0432 reduced the ratio of Bax/Bcl-2 and suppressed the expression of cleaved caspase-3, both of which were increased in the heart of the EAM rats, suggesting an anti-apoptotic role of Ro-32-0432. Besides, Ro-32-0432 suppressed EAM-induced cardiac fibrosis and release of pro-inflammatory cytokines IL-1β and IL-17. These results suggest that inhibition of PKC may serve as a potential therapeutic strategy for the treatment of myocarditis.

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Research Papers:

Effect of PKC inhibitor on experimental autoimmune myocarditis in Lewis rats

Abstract