PMID- 25892961 OWN - NLM STAT- MEDLINE DCOM- 20160111 LR - 20220408 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 11 IP - 5 DP - 2015 TI - Brain-derived neurotrophic factor regulates TRPC3/6 channels and protects against myocardial infarction in rodents. PG - 536-45 LID - 10.7150/ijbs.10754 [doi] AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is associated with coronary artery diseases. However, its role and mechanism in myocardial infarction (MI) is not fully understood. METHODS: Wistar rat and Kunming mouse model of MI were induced by the ligation of left coronary artery. Blood samples were collected from MI rats and patients. Plasma BDNF level, protein expression of BDNF, tropomyosin-related kinase B (TrkB) and its downstream transient receptor potential canonical (TRPC)3/6 channels were examined by enzyme-linked immunosorbent assay and Western blot. Infarct size, cardiac function and cardiomyocyte apoptosis were measured after intra-myocardium injection with recombinant human BDNF. Protective role of BDNF against cardiomyocyte apoptosis was confirmed by BDNF scavenger TrkB-Fc. The regulation of TRPC3/6 channels by BDNF was validated by pretreating with TRPC blocker (2-Aminoethyl diphenylborinate, 2-APB) and TRPC3/6 siRNAs. RESULTS: Circulating BDNF was significantly enhanced in MI rats and patients. Protein expression of BDNF, TrkB and TRPC3/6 channels were upregulated in MI. 3 days post-MI, BDNF treatment markedly reduced the infarct size and serum lactate dehydrogenase activity. Meanwhile, echocardiography indicated that BDNF significantly improved cardiac function of MI mice. Furthermore, BDNF markedly inhibited cardiomyocyte apoptosis by upregulating Bcl-2 expression and downregulating caspase-3 expression and activity in ischemic myocardium. In neonatal rat ventricular myocytes, cell viability was dramatically increased by BDNF in hypoxia, which was restored by TrkB-Fc. Furthermore, protective role of BDNF against hypoxia-induced apoptosis was reversed by 2-APB and TRPC3/6 siRNAs. CONCLUSION: BDNF/TrkB alleviated cardiac ischemic injury and inhibited cardiomyocytes apoptosis by regulating TRPC3/6 channels, which provides a novel potential therapeutic candidate for MI. FAU - Hang, Pengzhou AU - Hang P AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. FAU - Zhao, Jing AU - Zhao J AD - 2. Department of Cardiology of the First Affiliated Hospital (Key Laboratory of Cardiac Diseases and Heart Failure), Harbin Medical University, Harbin 150001, China. FAU - Cai, Benzhi AU - Cai B AD - 3. Department of Pharmacology (State-Province Key Laboratories of Biomedicine- Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China. FAU - Tian, Shanshan AU - Tian S AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. FAU - Huang, Wei AU - Huang W AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. FAU - Guo, Jing AU - Guo J AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. FAU - Sun, Chuan AU - Sun C AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. FAU - Li, Yue AU - Li Y AD - 2. Department of Cardiology of the First Affiliated Hospital (Key Laboratory of Cardiac Diseases and Heart Failure), Harbin Medical University, Harbin 150001, China. FAU - Du, Zhimin AU - Du Z AD - 1. Institute of Clinical Pharmacology of the Second Affiliated Hospital (Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin Medical University, Harbin 150086, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Membrane Glycoproteins) RN - 0 (TRPC Cation Channels) RN - 0 (TRPC3 cation channel) RN - 0 (TRPC6 Cation Channel) RN - 0 (Trpc6 protein, mouse) RN - 0 (Trpc6 protein, rat) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) SB - IM MH - Aged MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Female MH - Gene Expression Regulation/physiology MH - Humans MH - Male MH - Membrane Glycoproteins/genetics/metabolism MH - Mice MH - Middle Aged MH - Myocardial Infarction/*metabolism/prevention & control MH - Myocardial Ischemia/metabolism MH - Protein-Tyrosine Kinases/genetics/metabolism MH - Rats MH - Rats, Wistar MH - TRPC Cation Channels/genetics/*metabolism MH - TRPC6 Cation Channel MH - Up-Regulation PMC - PMC4400385 OTO - NOTNLM OT - Apoptosis OT - Brain derived neurotrophic factor OT - Myocardial infarction OT - Transient receptor potential canonical channel OT - TrkB-Fc COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2015/04/22 06:00 MHDA- 2016/01/12 06:00 PMCR- 2015/01/01 CRDT- 2015/04/21 06:00 PHST- 2014/10/08 00:00 [received] PHST- 2015/02/23 00:00 [accepted] PHST- 2015/04/21 06:00 [entrez] PHST- 2015/04/22 06:00 [pubmed] PHST- 2016/01/12 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - ijbsv11p0536 [pii] AID - 10.7150/ijbs.10754 [doi] PST - epublish SO - Int J Biol Sci. 2015 Mar 25;11(5):536-45. doi: 10.7150/ijbs.10754. eCollection 2015.