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Cardioprotective effects of tanshinone IIA pretreatment via kinin B2 receptor-Akt-GSK-3β dependent pathway in experimental diabetic cardiomyopathy.
Cardiovasc Diabetol. 2011 Jan 13; 10:4.CD

Abstract

AIMS

Diabetic cardiomyopathy, characterized by myocardial structural and functional changes, is a specific cardiomyopathy develops in patients with diabetes mellitus. The present study was to investigate the role of kinin B2 receptor-Akt-glycogen synthase kinase (GSK)-3β signalling pathway in mediating the protective effects of tanshinone IIA (TSN) on diabetic cardiomyopathy.

METHODS AND RESULTS

Streptozocin (STZ) induced diabetic rats (n = 60) were randomized to receive TSN, TSN plus HOE140 (a kinin B2 receptor antagonist), or saline. Healthy Sprague-Dawley (SD) rats (n = 20) were used as control. Left ventricular function, myocardial apoptosis, myocardial ultrastructure, Akt, GSK-3β and NF-κB phosphorylation, the expression of TNF-α, IL-6 and myeloperoxidase (MPO) were examined. Cardiac function was well preserved as evidenced by increased left ventricular ejection fraction (LVEF) and ± dp/dt (maximum speed of contraction/relaxation), along with decreased myocardial apoptotic death after TSN administration. TSN pretreatment alleviated mitochondria ultrastructure changes. TSN also enhanced Akt and GSK-3β phosphorylation and inhibited NF-κB phosphorylation, resulting in decreased TNF-α, IL-6 and MPO activities. Moreover, pretreatment with HOE140 abolished the beneficial effects of TSN: a decrease in LVEF and ± dp/dt, an inhibition of cardiomyocyte apoptosis, a destruction of cardiomyocyte mitochondria cristae, a reduction of Akt and GSK-3β phosphorylation, an enhancement of NF-κB phosphorylation and an increase of TNF-α, IL-6 and MPO production.

CONCLUSION

These data indicated that TSN is cardioprotective in the context of diabetic cardiomyopathy through kinin B2 receptor-Akt-GSK-3β dependent pathway.

Authors+Show Affiliations

Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21232147

Citation

Sun, Dongdong, et al. "Cardioprotective Effects of Tanshinone IIA Pretreatment Via Kinin B2 receptor-Akt-GSK-3β Dependent Pathway in Experimental Diabetic Cardiomyopathy." Cardiovascular Diabetology, vol. 10, 2011, p. 4.
Sun D, Shen M, Li J, et al. Cardioprotective effects of tanshinone IIA pretreatment via kinin B2 receptor-Akt-GSK-3β dependent pathway in experimental diabetic cardiomyopathy. Cardiovasc Diabetol. 2011;10:4.
Sun, D., Shen, M., Li, J., Li, W., Zhang, Y., Zhao, L., Zhang, Z., Yuan, Y., Wang, H., & Cao, F. (2011). Cardioprotective effects of tanshinone IIA pretreatment via kinin B2 receptor-Akt-GSK-3β dependent pathway in experimental diabetic cardiomyopathy. Cardiovascular Diabetology, 10, 4. https://doi.org/10.1186/1475-2840-10-4
Sun D, et al. Cardioprotective Effects of Tanshinone IIA Pretreatment Via Kinin B2 receptor-Akt-GSK-3β Dependent Pathway in Experimental Diabetic Cardiomyopathy. Cardiovasc Diabetol. 2011 Jan 13;10:4. PubMed PMID: 21232147.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotective effects of tanshinone IIA pretreatment via kinin B2 receptor-Akt-GSK-3β dependent pathway in experimental diabetic cardiomyopathy. AU - Sun,Dongdong, AU - Shen,Min, AU - Li,Jiayi, AU - Li,Weijie, AU - Zhang,Yingmei, AU - Zhao,Li, AU - Zhang,Zheng, AU - Yuan,Yuan, AU - Wang,Haichang, AU - Cao,Feng, Y1 - 2011/01/13/ PY - 2010/12/11/received PY - 2011/01/13/accepted PY - 2011/1/15/entrez PY - 2011/1/15/pubmed PY - 2011/5/4/medline SP - 4 EP - 4 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 10 N2 - AIMS: Diabetic cardiomyopathy, characterized by myocardial structural and functional changes, is a specific cardiomyopathy develops in patients with diabetes mellitus. The present study was to investigate the role of kinin B2 receptor-Akt-glycogen synthase kinase (GSK)-3β signalling pathway in mediating the protective effects of tanshinone IIA (TSN) on diabetic cardiomyopathy. METHODS AND RESULTS: Streptozocin (STZ) induced diabetic rats (n = 60) were randomized to receive TSN, TSN plus HOE140 (a kinin B2 receptor antagonist), or saline. Healthy Sprague-Dawley (SD) rats (n = 20) were used as control. Left ventricular function, myocardial apoptosis, myocardial ultrastructure, Akt, GSK-3β and NF-κB phosphorylation, the expression of TNF-α, IL-6 and myeloperoxidase (MPO) were examined. Cardiac function was well preserved as evidenced by increased left ventricular ejection fraction (LVEF) and ± dp/dt (maximum speed of contraction/relaxation), along with decreased myocardial apoptotic death after TSN administration. TSN pretreatment alleviated mitochondria ultrastructure changes. TSN also enhanced Akt and GSK-3β phosphorylation and inhibited NF-κB phosphorylation, resulting in decreased TNF-α, IL-6 and MPO activities. Moreover, pretreatment with HOE140 abolished the beneficial effects of TSN: a decrease in LVEF and ± dp/dt, an inhibition of cardiomyocyte apoptosis, a destruction of cardiomyocyte mitochondria cristae, a reduction of Akt and GSK-3β phosphorylation, an enhancement of NF-κB phosphorylation and an increase of TNF-α, IL-6 and MPO production. CONCLUSION: These data indicated that TSN is cardioprotective in the context of diabetic cardiomyopathy through kinin B2 receptor-Akt-GSK-3β dependent pathway. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/21232147/Cardioprotective_effects_of_tanshinone_IIA_pretreatment_via_kinin_B2_receptor_Akt_GSK_3β_dependent_pathway_in_experimental_diabetic_cardiomyopathy_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-10-4 DB - PRIME DP - Unbound Medicine ER -