title: Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression.
abstract: Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive left ventricular remodeling whose clinical manifestations and molecular basis are poorly understood. We aimed to evaluate the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage IDCM. Expression patterns of 8 mechanoptotic machinery-associated titin ligands (ANKRD1, ANKRD2, TRIM63, TRIM55, NBR1, MLP, FHL2, and TCAP) were quantitated in endomyocardial biopsies from 25 patients with advanced IDCM. When comparing NYHA disease stages, elevated ANKRD1 expression levels marked transition from NYHA < IV to NYHA IV. ANKRD1 expression levels closely correlated with systolic strain depression and short E wave deceleration time, as determined by echocardiography. On molecular level, myocardial ANKRD1 and serum adiponectin correlated with low BAX/BCL-2 ratios, indicative of antiapoptotic tissue propensity observed during the worsening of heart failure. ANKRD1 is a potential marker for cardiac remodeling and disease progression in IDCM. ANKRD1 expression correlated with reduced cardiac contractility and compliance. The association of ANKRD1 with antiapoptotic response suggests its role as myocyte survival factor during late stage heart disease, warranting further studies on ANKRD1 during end-stage heart failure.
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany ; Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, M. K. Ciurlionio g. 21, LT-03101 Vilnius, Lithuania.
authors.forename: Julius
authors.initials: J
authors.lastname: Bogomolovas
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Brohm
authors.affiliation: Vilnius University Hospital Santariskiu Klinikos, Santariškiu g. 2, LT-08661 Vilnius, Lithuania.
authors.forename: Jelena
authors.initials: J
authors.lastname: Čelutkienė
authors.affiliation: Vilnius University Hospital Santariskiu Klinikos, Santariškiu g. 2, LT-08661 Vilnius, Lithuania.
authors.forename: Giedrė
authors.initials: G
authors.lastname: Balčiūnaitė
authors.affiliation: State Research Institute, Center for Innovative Medicine, Department of Stem Cell Biology, Žygimantu g. 9, LT-01102 Vilnius, Lithuania.
authors.forename: Daiva
authors.initials: D
authors.lastname: Bironaitė
authors.affiliation: Vilnius University Institute of Biochemistry, Mokslininku g. 12, LT-08660 Vilnius, Lithuania.
authors.forename: Virginija
authors.initials: V
authors.lastname: Bukelskienė
authors.affiliation: Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, M. K. Ciurlionio g. 21, LT-03101 Vilnius, Lithuania.
authors.forename: Dainius
authors.initials: D
authors.lastname: Daunoravičus
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Witt
authors.affiliation: Experimental and Clinical Research Center (ECRC), Max-Delbrueck Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10, Buch, 13125 Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fielitz
authors.affiliation: Department of Pathology, Forensic Medicine and Pharmacology, Faculty of Medicine, Vilnius University, M. K. Ciurlionio g. 21, LT-03101 Vilnius, Lithuania.
authors.forename: Virginija
authors.initials: V
authors.lastname: Grabauskienė
authors.affiliation: Department of Integrative Pathophysiology, Medical Faculty Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Labeit
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D064752:Atrial Remodeling; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000473:pathology; D064211:Connectin / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C491304:ANKRD1 protein, human; D052242:Adiponectin; D064211:Connectin; D008024:Ligands; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins