Cardiac microvascular barrier function mediates the protection of Tongxinluo against myocardial ischemia/reperfusion injury.

Abstract

OBJECTIVE:

Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network.

MATERIALS AND METHODS:

To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed.

RESULTS:

Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI.

CONCLUSIONS:

Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC.

• Authors: Kang Qi, Lujin Li, Xiangdong Li, Jinglin Zhao, Yang Wang, Shijie You, Fenghuan Hu, Haitao Zhang, Yutong Cheng, Sheng Kang, Hehe Cui, Lian Duan, Chen Jin, Qingshan Zheng, Yuejin Yang
• Journal: PloS one (PLoS One) Vol. 10 Issue 3 Pg. e0119846 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25781461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Drugs, Chinese Herbal
• tongxinluo

Topics

• Animals
• Cardiotonic Agents (therapeutic use)
• Drugs, Chinese Herbal (therapeutic use)
• Female
• Heart (drug effects)
• Hemodynamics (drug effects)
• Ischemic Preconditioning
• Male
• Models, Theoretical
• Myocardium (pathology)
• No-Reflow Phenomenon
• Principal Component Analysis
• Reperfusion Injury (drug therapy, pathology)
• Swine