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In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null ( Lrrc10<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10<jats:sup>\u2212\/\u2212<\/jats:sup>mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10<jats:sup>\u2212\/\u2212<\/jats:sup>cardiomyocytes also exhibited reduced contractility in response to \u03b2-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His<jats:sup>150<\/jats:sup>of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis.<\/jats:p>","DOI":"10.1152\/ajpheart.00717.2014","type":"journal-article","created":{"date-parts":[[2015,11,26]],"date-time":"2015-11-26T04:01:34Z","timestamp":1448510494000},"page":"H269-H278","source":"Crossref","is-referenced-by-count":28,"title":["LRRC10 is required to maintain cardiac function in response to pressure overload"],"prefix":"10.1152","volume":"310","author":[{"given":"Matthew J.","family":"Brody","sequence":"first","affiliation":[{"name":"Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin;"},{"name":"Molecular and Environmental Toxicology Center, School of Medicine and 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