title: Relaxin-2 improves diastolic function of pressure-overloaded rats via phospholamban by activating Akt.
abstract: BACKGROUND
  Relaxin is a peptide hormone which has been demonstrated to be safe and has a therapeutic effect on acute heart failure in clinic trials. However, its effect on diastolic function is still unknown. The aims of the study were to determine whether relaxin could improve the diastolic function in pressure-overloaded rat model and to analyze potential mechanisms.
  
  
  RESULTS
  In the present study, a pressure-overloaded rat model induced by transaortic constriction (TAC) was established. Four weeks after TAC, echocardiography was performed and then all the rat models were randomly divided into 3 groups: models without intramyocardial injection (TAC), with intramyocardial injection of empty adenoviral vector (TAC+GFP) and adenoviral vector overexpression relaxin-2 gene (TAC+RLN2). A sham group was also included. Twelve days after intramyocardial injection, echocardiography and hemodynamics were carried out to evaluate diastolic function in sham, TAC, TAC+GFP and TAC+RLN2 groups. Then hearts were harvested for subsequent examinations. The results indicated that relaxin-2 had ameliorated diastolic function in the pressure-overloaded rats. Compared with the TAC and TAC+GFP groups, the relaxin-2 gene transfer increased phosphorylation of Akt at both the Ser473 and Thr308 sites. Meanwhile, it increased the Ser16 and Thr17- phosphorylation levels of phospholamban (PLB). Furthermore, SERCA2 activity was enhanced in the TAC+RLN2 group more than in the TAC and TAC+GFP groups.
  
  
  CONCLUSIONS
  These results demonstrated that relaxin-2 gene therapy improved diastolic function in pressure-overloaded rats. The potential mechanism may be that relaxin-2 gene transfer enhances SERCA2 activity in hearts by increasing phospholamban phosphorylation through nuclear-targeted Akt phosphorylation.
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Shuai
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yi-di
authors.initials: YD
authors.lastname: Meng
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: yongxin_lu6@aliyun.com.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Su
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Tao
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Su-Dan
authors.initials: SD
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006332:Cardiomegaly / Q000235:genetics / Q000628:therapy*; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D012065:Relaxin / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt; D012065:Relaxin; D000099211:Phospholamban
keywords: Diastolic function; Nuclear-target Akt; Phospholamban; Relaxin