title: Paricalcitol Attenuates Cardiac Fibrosis and Expression of Endothelial Cell Transition Markers in Isoproterenol-Induced Cardiomyopathic Rats.
abstract: Acute cardiomyopathy is a health problem worldwide. Few studies have shown an association between acute cardiomyopathy and low vitamin D status. Paricalcitol, a vitamin D receptor activator, clinically benefits patients with advanced kidney disease. The effect of paricalcitol supplement on cardiac remodeling in cardiomyopathic rats is unknown. This experimental study investigated the effect of paricalcitol in rats with cardiomyopathy induced by isoproterenol.
  
  
  
  Prospective, randomized, controlled experimental study.
  
  
  
  Hospital-affiliated animal research institution.
  
  
  
  Eight-week-old male Wistar-Kyoto rats.
  
  
  
  Male Wistar-Kyoto rats were first injected intraperitoneally with isoproterenol to create a rat model of acute cardiomyopathy. Then paricalcitol was administered intraperitoneally to isoproterenol-injected rats at a dosage of 200 ng three times a week for 3 weeks. Relevant cardiomyopathy-related variables were measured regularly in three groups of rats, controls, isoproterenol, and isoproterenol plus paricalcitol. Rat hearts were obtained for evaluation of cardiac fibrosis using Masson trichrome staining and commercially available software, and evaluation of cell transition using immunofluorescence staining analysis.
  
  
  
  Isoproterenol infusions generated significant cardiac fibrosis (p < 0.001). Subsequent paricalcitol treatment attenuated the isoproterenol-induced cardiac fibrosis (p = 0.006). Fluorescence showed colocalization of endothelial and fibroblast cell markers (cluster differentiation 31 and α-smooth muscle actin, respectively) in the isoproterenol-treated hearts. Paricalcitol injections attenuated the isoproterenol-induced fluorescence intensity of two cell markers (p < 0.01).
  
  
  
  Paricalcitol injections may ameliorate isoproterenol-induced cardiac fibrosis possibly through regulating cell transition.
authors.affiliation: 1Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.2Cardiovascular Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.3Department of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.4School of Medicine, National Yang-Ming University, Taipei, Taiwan.5Department of Administration, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.6Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.7Institute of Clinical Medicine, National Cheng-Kung University, Tainan, Taiwan.8Genomics Research Center, Academia Sinica, Taipei, Taiwan.9Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.10Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.11Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lai
authors.forename: Chun-Peng
authors.initials: CP
authors.lastname: Liu
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Cheng
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Wen-Hsien
authors.initials: WH
authors.lastname: Lu
authors.forename: Gwo-Ching
authors.initials: GC
authors.lastname: Sun
authors.forename: Jau-Cheng
authors.initials: JC
authors.lastname: Liou
authors.forename: Ching-Jiunn
authors.initials: CJ
authors.lastname: Tseng
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D042783:Endothelial Cells; D058750:Epithelial-Mesenchymal Transition; D004872:Ergocalciferols / Q000627:therapeutic use*; D005355:Fibrosis; D007545:Isoproterenol; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D000199:Actins; D004872:Ergocalciferols; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C084656:paricalcitol; D007545:Isoproterenol