Limits...
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

Scatterplot for observational values of necrosis and no-reflow sizes in the model group and all intervention groups.A: Scatterplot for necrosis sizes and no-reflow sizes; B: Scatterplot and established model. Under similar no-reflow sizes, differences in necrosis size existed with different interventions. Diltiazem and verapamil reduce no-reflow size and necrosis size to a similar degree. IPC, verapamil and diltiazem reduced no-reflow size to a similar degree, but IPC caused a greater decrease in necrosis size than diltiazem or verapamil.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4363146&req=5

pone.0119846.g004: Scatterplot for observational values of necrosis and no-reflow sizes in the model group and all intervention groups.A: Scatterplot for necrosis sizes and no-reflow sizes; B: Scatterplot and established model. Under similar no-reflow sizes, differences in necrosis size existed with different interventions. Diltiazem and verapamil reduce no-reflow size and necrosis size to a similar degree. IPC, verapamil and diltiazem reduced no-reflow size to a similar degree, but IPC caused a greater decrease in necrosis size than diltiazem or verapamil.

Mentions: To quantitatively compare the effects of different interventions on the severity of lethal IRI, observational values of necrosis size and no-reflow size from all intervention groups were displayed in Fig. 4A, B. Lethal IRI severity was evaluated by pathological staining with or without mathematical modeling respectively. In the model-based pathological approach, NRS was introduced and calculated as follows: NRS = observational necrosis size—estimated necrosis size. Alternatively, in the simple pathological approach, lethal IRI was calculated as previously described [26], with modification: IRI = observational necrosis size—observational no-reflow size (Fig. 5A). Then the association between NRS and IRI was tested by Spearman correlation analysis.


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)

Scatterplot for observational values of necrosis and no-reflow sizes in the model group and all intervention groups.A: Scatterplot for necrosis sizes and no-reflow sizes; B: Scatterplot and established model. Under similar no-reflow sizes, differences in necrosis size existed with different interventions. Diltiazem and verapamil reduce no-reflow size and necrosis size to a similar degree. IPC, verapamil and diltiazem reduced no-reflow size to a similar degree, but IPC caused a greater decrease in necrosis size than diltiazem or verapamil.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119846.g004: Scatterplot for observational values of necrosis and no-reflow sizes in the model group and all intervention groups.A: Scatterplot for necrosis sizes and no-reflow sizes; B: Scatterplot and established model. Under similar no-reflow sizes, differences in necrosis size existed with different interventions. Diltiazem and verapamil reduce no-reflow size and necrosis size to a similar degree. IPC, verapamil and diltiazem reduced no-reflow size to a similar degree, but IPC caused a greater decrease in necrosis size than diltiazem or verapamil.
Mentions: To quantitatively compare the effects of different interventions on the severity of lethal IRI, observational values of necrosis size and no-reflow size from all intervention groups were displayed in Fig. 4A, B. Lethal IRI severity was evaluated by pathological staining with or without mathematical modeling respectively. In the model-based pathological approach, NRS was introduced and calculated as follows: NRS = observational necrosis size—estimated necrosis size. Alternatively, in the simple pathological approach, lethal IRI was calculated as previously described [26], with modification: IRI = observational necrosis size—observational no-reflow size (Fig. 5A). Then the association between NRS and IRI was tested by Spearman correlation analysis.

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