title: Role of cardiac myofilament proteins titin and collagen in the pathogenesis of diastolic dysfunction in cirrhotic rats.
abstract: OBJECTIVE
  Significance of diastolic dysfunction in cirrhotic cardiomyopathy has been brought to the forefront with several reports of unexpected heart failure following liver transplantation and transjugular intrahepatic portosystemic stent-shunt, but the etiology remains unclear. The present study investigated the role of passive tension regulators - titin and collagen - in the pathogenesis of this condition.
  
  
  METHODS
  Cirrhosis was induced by bile duct ligation (BDL) in rats, while controls underwent bile duct inspection with no ligation. Four weeks after operation, cardiac mRNA and protein levels of titin, collagen, and protein kinase A (PKA) were determined. Diastolic function was examined in isolated right ventricular cardiomyocytes, while passive tension was examined in right ventricular trabeculae muscles.
  
  
  RESULTS
  In BDL animals, diastolic return velocity was significantly decreased, relaxation time increased and passive tension increased. However, no significant difference in mRNA and protein levels of titin was observed. PKA mRNA and protein levels were significantly decreased in BDL animals. Collagen levels were also significantly altered in the BDL group.
  
  
  CONCLUSIONS
  Therefore, diastolic dysfunction exists in cirrhosis with alterations in titin modulation, PKA levels, and collagen configuration contributing to the pathogenesis of this condition.
authors.affiliation: Liver Unit, GI Research Group, Calgary, Canada. tamig81@yahoo.com
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Glenn
authors.forename: Hooman
authors.initials: H
authors.lastname: Honar
authors.forename: Hongqun
authors.initials: H
authors.lastname: Liu
authors.forename: Henk E D J
authors.initials: HE
authors.lastname: ter Keurs
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D009202:Cardiomyopathies / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D064211:Connectin; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D054144:Heart Failure, Diastolic / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D064211:Connectin; D017931:DNA Primers; D009124:Muscle Proteins; D012333:RNA, Messenger; C577295:Ttn protein, rat; D003094:Collagen; D017868:Cyclic AMP-Dependent Protein Kinases