title: Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis.
abstract: OBJECTIVE
  Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism.
  
  
  METHODS
  Adult male mice were randomly assigned to Control group (kept at room temperature), Cold group (kept at low air temperature range from 3°C to 5°C) and Resveratrol treatment group (100mg/kg/day) for eight weeks. HE staining, Masson staining and Transmission electron microscopy were employed to detect cardiac structure, fibrosis and myocardial ultrastructure, respectively. Echocardiogram was used to measure myocardial functions. Western blot was used to detect the expression of MAPK pathway and apoptotic proteins. TUENL assay was performed to evaluate cardiomyocyte apoptosis. qRT-PCR was employed to measure the mRNA level.
  
  
  RESULTS
  Cold-treated mice showed a higher heart/body weight ratio and heart weight/tibia length ratio compared with control mice, and Resveratrol treatment may suppress these changes in cold-treated mice. Myocardial cross-section area and cardiac collagen volume were larger in cold group than control group, which also can be attenuated by Resveratrol treatment. Also, Resveratrol improved the ultrastructure damage of myocardium such as myofibril disarray in cold group. Echocardiogram measurement showed that EF and FS values in cold group declined apparently as compared to control group, and Resveratrol may improve the reduction of heart functions. The expression of p-JNK, p-p38 and p-ERK relative to total JNK, p38 and ERK in cold group was not altered in cold group and Resveratrol group as compared to control group. Cold-treated mouse hearts also showed the upregulation of hypertrophy-related miRNA-miR-328 but not miR-23a, and Resveratrol treatment can inhibit the increase of miR-328. Finally, Resveratrol treatment also may suppress apoptosis of myocardium in cold-treated mouse hearts via inhibiting Bax and caspase-3 activation.
  
  
  CONCLUSIONS
  In summary, low ambient temperature can cause enlarged heart, ultrastructure damage of myocardium and weakened functions, and Resveratrol treatment effectively suppressed these changes at least partially via inhibiting cardiomyocyte apoptosis.
authors.affiliation: Department of Pharmacology (Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yin
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Wenya
authors.initials: W
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Chongwei
authors.initials: C
authors.lastname: Bi
authors.forename: Hongyang
authors.initials: H
authors.lastname: Chen
authors.forename: Xingda
authors.initials: X
authors.lastname: Li
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Benzhi
authors.initials: B
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003080:Cold Temperature / Q000009:adverse effects*; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D013267:Stilbenes; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D000077185:Resveratrol