title: Increases of desmin and α-actinin in mouse cardiac myofibrils as a response to diastolic dysfunction.
abstract: Up-regulation of desmin has been reported in cardiac hypertrophy and failure but the pathophysiological cause and significance remain to be investigated. By examining genetically modified mouse models representative for diastolic or systolic heart failure, we found significantly increased levels of desmin and α-actinin in the myofibrils of hearts with impaired diastolic function but not hearts with weakened systolic function. The increased desmin and α-actinin are mainly found in myofibrils at the Z-disks. Two weeks of transverse aortic constriction (TAC) induced increases of desmin and α-actinin in mouse hearts of occult diastolic failure but not in wild type or transgenic mouse hearts with mildly lowered systolic function or with increased diastolic function. The chronic or TAC-induced increase of desmin showed no proportional increase in phosphorylation, implicating an up-regulated expression rather than a decreased protein turnover. The data demonstrate a novel early response specifically to diastolic heart failure, indicating a function of the Z-disk in the challenging clinical condition of heart failure with preserved ejection fraction (HFpEF).
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Sheng
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Feng
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Pinto
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: jjin@med.wayne.edu.
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000220:Adaptation, Biological; D000818:Animals; D015415:Biomarkers; D003893:Desmin / Q000378:metabolism*; D003971:Diastole; D004195:Disease Models, Animal; D004452:Echocardiography; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D013599:Systole; D018754:Ventricular Dysfunction / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D003893:Desmin; D000185:Actinin
keywords: Cardiac muscle sarcomere; Desmin; Diastolic heart failure; Thin filament regulatory proteins; Z-disk; α-Actinin