Effect of PKC inhibitor on experimental autoimmune myocarditis in Lewis rats

被引：15

作者：

Zhong, Chunlian ^{[1
]}

Wu, Yang ^{[1
,2
]}

Chang, He ^{[1
,2
]}

Liu, Chunxiao ^{[1
,2
]}

Zhou, Li ^{[1
]}

Zou, Jun ^{[1
]}

Qi, Zhi ^{[1
]}

机构：

[1] Xiamen Univ, Dept Basic Med Sci, Med Coll, Xiamen, Peoples R China

[2] Xiamen Univ, Xiamen Cardiovasc Hosp, Med Coll, Xiamen, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 33期

基金：

中国国家自然科学基金;

关键词：

myocarditis; PKC signaling; PKC inhibitor; apoptosis; inflammation; PROTEIN-KINASE-C; INDUCED HEART-FAILURE; THERAPEUTIC TARGET; PHARMACOLOGICAL INHIBITION; CARDIAC CONTRACTILITY; EPSILON-PKC; DELTA-PKC; T-CELLS; DYSFUNCTION; APOPTOSIS;

D O I：

10.18632/oncotarget.17018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-a 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-1 beta and IL-17. These results suggest that inhibition of PKC may serve as a potential therapeutic strategy for the treatment of myocarditis.

引用

页码：54187 / 54198

页数：12

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