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

Qi K, Li L, Li X, Zhao J, Wang Y, You S, Hu F, Zhang H, Cheng Y, Kang S, Cui H, Duan L, Jin C, Zheng Q, Yang Y - PLoS ONE (2015)

Bottom Line: IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively.Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively).Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

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.

No MeSH data available.


Related in: MedlinePlus

Data sources.Data from our 19 previous studies were used for mathematical modeling only. Data from our present experiment were used for calculating NRS and investigating mechanism of IPC and TXL. Abbreviations: NRS = necrosis reduction space; IPC = ischemia preconditioning; PCA = principal component analysis.
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pone.0119846.g001: Data sources.Data from our 19 previous studies were used for mathematical modeling only. Data from our present experiment were used for calculating NRS and investigating mechanism of IPC and TXL. Abbreviations: NRS = necrosis reduction space; IPC = ischemia preconditioning; PCA = principal component analysis.

Mentions: The data in this study had two sources (Fig. 1). Our 19 previous animal studies offered the data for mathematical modeling only. And data from our present experiment with 168 animals were used for lethal IRI severity evaluation, principal component analysis (PCA) and consequent mechanism investigation of TXL.


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

Qi K, Li L, Li X, Zhao J, Wang Y, You S, Hu F, Zhang H, Cheng Y, Kang S, Cui H, Duan L, Jin C, Zheng Q, Yang Y - PLoS ONE (2015)

Data sources.Data from our 19 previous studies were used for mathematical modeling only. Data from our present experiment were used for calculating NRS and investigating mechanism of IPC and TXL. Abbreviations: NRS = necrosis reduction space; IPC = ischemia preconditioning; PCA = principal component analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363146&req=5

pone.0119846.g001: Data sources.Data from our 19 previous studies were used for mathematical modeling only. Data from our present experiment were used for calculating NRS and investigating mechanism of IPC and TXL. Abbreviations: NRS = necrosis reduction space; IPC = ischemia preconditioning; PCA = principal component analysis.
Mentions: The data in this study had two sources (Fig. 1). Our 19 previous animal studies offered the data for mathematical modeling only. And data from our present experiment with 168 animals were used for lethal IRI severity evaluation, principal component analysis (PCA) and consequent mechanism investigation of TXL.

Bottom Line: IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively.Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively).Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.

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.

No MeSH data available.


Related in: MedlinePlus