title: Role of HSF1-upregulated AC6 in ameliorating heart failure in mice.
abstract: OBJECTIVE
  Our previous studies discovered that Heat shock factor 1(HSF1) can alleviate pressure overload induced heart failure in mice. However, its molecular mechanisms are yet to be further explained. Many studies have already verified that Adenylyl Cyclase 6 (AC6) can ameliorate heart failure, but it is still unknown whether or not the pathway HSF1 is involved in the process. Our preliminary experiment showed that the expression level of AC6 is positively associated with HSF1. Therefore, in the present study, we aimed to explore whether HSF1 can play its role in ameliorating heart failure by regulating AC6, and how the potential internal mechanisms work.
  
  
  METHODS
  We applied the Transverse Aortic Constriction (TAC) for 4 weeks to develop the C57BL/6 mice pressure overload induced heart failure model. First, the mice were divided into TAC group and SHAM group. Changes in the cardiac function and morphology of the mice were observed by an ultrasonic device and Masson staining slices, expressions of AC6 mRNA were observed by RT-QPCR, expressions of HSF1 and proteinkinase A (PKA) were examined by Western Blotting, and the levels of cyclic adenosine monophosphate (cAMP) from aortic blood were measured by ELISA. Second, the TAC group were further divided into subgroups of HSF1 transgene mice, HSF1 knockout mice and wild type mice, followed by the aforesaid observations.
  
  
  RESULTS
  In the SHAM group, no obvious variations of cardiac function, AC6 mRNAHSF1, PKA, cAMP and other test results were found among each of the subgroups. Compared to the SHAM group, the TAC group presented clearly weakened heart functions, while, expressions of AC6 mRNA, HSF1, PKA and cAMP all recorded obvious increases. In the TAC group, compared to the WT subgroup, the HSF1 KO subgroup presented decreases in expressions of AC6 mRNA, HSF1, PKA and cAMP, and at the same time, the heart functions were weaker, while, the HSF1 TG subgroup recorded the contrary results.
  
  
  CONCLUSIONS
  In the pressure overload heart failure model, HSF1 can ameliorate heart failure by positively regulating the pathway of AC6/cAMP/PKA.
authors.affiliation: Key Laboratory of Arrhythmias of the Ministry of Education of China, and Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Erlinda
authors.initials: E
authors.lastname: The
authors.affiliation: Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Peizhao
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Yaowei
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Fangjie
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. Electronic address: ljm5031@easthospital.cn.
authors.forename: Jiming
authors.initials: J
authors.lastname: Li
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004562:Electrocardiography; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D000076249:Heat Shock Transcription Factors; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6
keywords: AC6; HSF1; Heart failure; PKA; cAMP