期刊
MICROVASCULAR RESEARCH
卷 80, 期 1, 页码 158-165出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2010.01.003
关键词
Diabetes; Cardiac microvascular endothelial cells (CMECs); PKC-beta inhibitor; Permeability
资金
- National Natural Science Foundation of China (NSFC) [30770784, 30670969]
- Xijing Research Boosting Program [XJZT07Z05, XJZT08Z04]
The PKC-beta inhibitor ruboxistaurin (RBX or LY333531) prevents diabetic renal and retinal microvascular complications. However, the effect of RBX on diabetic cardiac microvascular dysfunction is still unclear. In this study, we aimed to investigate the effects and mechanisms of RBX treatment upon cardiac endothelial barrier dysfunction in high glucose states. We demonstrated RBX treatment suppressed high glucose induced PKC-beta II activation and phosphorylation of beta-catenin in vivo and in vitro experiments. Meanwhile, RBX treatment protected cardiac microvascular barrier function in diabetic animals and monolayer barrier function of cultured cardiac microvascular endothelial cells (CMECs), reproducing the same effect as PKC-beta II siRNA. These results provide new insight into protective properties of PKC-beta inhibitor against cardiac endothelial barrier dysfunction. PKC-beta inhibitor RBX prevented chronic cardiac microvascular barrier dysfunction and improved endothelial cell-cell junctional function in high glucose states. (C) 2010 Elsevier Inc. All rights reserved.
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