Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease

PloS One
Analyne SchroederChristopher S Colwell

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 dis...Continue Reading

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Citations

Jul 1, 2017·Nature Reviews. Cardiology·Robert H Henning, Bianca J J M Brundel
Jun 4, 2017·Physiological Reports·Tamara S CutlerChristopher S Colwell
Aug 8, 2018·Journal of Biological Rhythms·Daniel S WhittakerChristopher S Colwell
Sep 1, 2018·Journal of Neuroscience Research·Dika KuljisChristopher S Colwell
Jun 8, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Jorge Espinoza-DeroutTheodore C Friedman
Jul 31, 2019·Journal of Neuroscience Research·Benjamin SmarrChristopher S Colwell
Oct 9, 2019·Journal of Huntington's Disease·Rachel Y CheongÅsa Petersén
Jan 4, 2020·Acta Biochimica Et Biophysica Sinica·Mingjie YangJun Ren
Oct 19, 2016·Journal of Neuroscience Research·Volkan Coskun, Dawn M Lombardo
Jun 8, 2018·Frontiers in Physiology·Bethan J CritchleyMichal Mielcarek
Jan 3, 2021·Life Sciences·Julliane Vasconcelos Joviano-SantosDanilo Roman-Campos
Mar 17, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Akanksha Singh, Namita Agrawal
May 13, 2021·Ageing Research Reviews·Chia-Lung Chuang, Fabio Demontis
Jul 16, 2019·Life Sciences·Priscila Aparecida Costa ValadãoAline Silva de Miranda

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Methods Mentioned

BETA
transgenic
PCR
Genotyping
chips
Protein Assay
RNA-Seq

Software Mentioned

IPA
NIH Image
Bioconductor
Ingenuity Pathway Analysis ( IPA
Corel Draw
AxioVision
HEM
LIMMA ( Linear Models for Microarray and RNA - Seq Data )
Primer3
BeadStudio

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