title: Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease.
abstract: While Huntington's disease (HD) is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Analyne M
authors.initials: AM
authors.lastname: Schroeder
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Huei Bin
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Saemi
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Physiology and Cardiovascular Research Lab, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Jordan
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Fuying
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Department of Physiology and Cardiovascular Research Lab, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Roos
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.|Department of Pathology & Laboratory Medicine, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Ghiani
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California Los Angeles, Los Angeles, California, 90095-1751, United States of America.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000375:Aging; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D005355:Fibrosis; D020869:Gene Expression Profiling; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060885:Multiplex Polymerase Chain Reaction; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D046888:Tissue Array Analysis; D019680:Trinucleotide Repeat Expansion; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*
chemical_list: D000318:Adrenergic beta-Agonists; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D007545:Isoproterenol