PLoS ONE (Jan 2015)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0119846
Journal volume & issue
Vol. 10, no. 3
p. e0119846

Abstract

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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.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.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, P0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI.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.