title: Tanshinone IIA protects against cardiac hypertrophy via inhibiting calcineurin/NFATc3 pathway.
abstract: Pathological cardiac hypertrophy induced by adrenergic overactivation can subsequently develop to heart failure which remains as a leading cause of mortality worldwide. Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of the Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. However, little is know about the effect of Tanshinone IIA on cardiac hypertrophy. The present study was aimed to investigate whether Tanshinone IIA prevents cardiac hypertrophy induced by isoproterenol (ISO) and to clarify its possible mechanisms. Cardiomyocytes hypertrophy was induced by ISO 10 μM for 48 h with or without Tanshinone IIA 10, 30, 100 μM pretreatment, and evaluated by determining the cell size and the expression of ANP, BNP, β-MHC, Calcineurin, and NFATc3 by real-time PCR and western blot. We found that Tanshinone IIA pretreatment attenuated the enlargement of cell surface area induced by ISO in cultured cardiomyocytes. The mRNA level of ANP, BNP and β-MHC was obviously elevated in ISO-treated cardiac cells, which was effectively inhibited by Tanshinone IIA. Moreover, we found that Tanshinone IIA pretreatment could prevent the augment of intracellular calcium transient in ISO-treated cardiomyocytes. The further study revealed that Calcineurin, NFATc3, ANP, BNP and β-MHC proteins were upregulated by ISO in ventricular myocytes, and Tanshinone IIA pretreatment significantly attenuate the increased expression of Calcineurin, NFATc3, ANP, BNP and β-MHC proteins. In summary, Tanshinone IIA attenuated cardiomyocyte hypertrophy induced by ISO through inhibiting Calcineurin/NFATc3 pathway, which provides new insights into the pharmacological role and therapeutic mechanism of Tanshinone IIA in heart diseases.
authors.affiliation: Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Tan
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Xinyue
authors.initials: X
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Benzhi
authors.initials: B
authors.lastname: Cai
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
authors.forename: Deli
authors.initials: D
authors.lastname: Dong
authors.forename: Yanju
authors.initials: Y
authors.lastname: Liu
authors.forename: Xingda
authors.initials: X
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Xueqi
authors.initials: X
authors.lastname: Li
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
mesh_terms: D045784:Abietanes / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007545:Isoproterenol; D008516:Medicine, Chinese Traditional; D032383:Myocytes, Cardiac / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D045784:Abietanes; D004365:Drugs, Chinese Herbal; C000594638:MYH7 protein, rat; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; C021751:tanshinone; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019703:Calcineurin; D018995:Myosin Heavy Chains; D007545:Isoproterenol