Dissemin is shutting down on January 1st, 2025

Published in

Public Library of Science, PLoS ONE, 1(11), p. e0147269, 2016

DOI: 10.1371/journal.pone.0147269

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

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.