title: Calreticulin induces dilated cardiomyopathy.
abstract: BACKGROUND
  Calreticulin, a Ca(2+)-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.
  
  
  RESULTS
  We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca(2+) signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca(2+)-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca(2+)-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.
  
  
  CONCLUSIONS
  We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca(2+) handling genes, gap junction components and left ventricle remodeling.
authors: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors: Dukgyu
authors: D
authors: Lee
authors: Tatsujiro
authors: T
authors: Oka
authors: Beth
authors: B
authors: Hunter
authors: Alison
authors: A
authors: Robinson
authors: Sylvia
authors: S
authors: Papp
authors: Kimitoshi
authors: K
authors: Nakamura
authors: Wattamon
authors: W
authors: Srisakuldee
authors: Barbara E
authors: BE
authors: Nickel
authors: Peter E
authors: PE
authors: Light
authors: Jason R B
authors: JR
authors: Dyck
authors: Gary D
authors: GD
authors: Lopaschuk
authors: Elissavet
authors: E
authors: Kardami
authors: Michal
authors: M
authors: Opas
authors: Marek
authors: M
authors: Michalak
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D037282:Calreticulin / Q000378:metabolism*; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002645:Chickens; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D004562:Electrocardiography; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D014463:Ultrasonography
chemical_list: D037282:Calreticulin; D002155:Calsequestrin; D017630:Connexins; D012333:RNA, Messenger; D018995:Myosin Heavy Chains