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Regulatory changes in the α-cardiac actin variants H88Y and F90Δ implicated in early-onset hypertrophic cardiomyopathy

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Title: Regulatory changes in the α-cardiac actin variants H88Y and F90Δ implicated in early-onset hypertrophic cardiomyopathy
Author: Shaikh, Zeeshan
Department: Department of Molecular and Cellular Biology
Program: Molecular and Cellular Biology
Advisor: Dawson, John
Abstract: Cardiovascular disease (CVD) impacts millions of lives affecting 1 in 12 Canadians over the age of 20 between 2012 and 2013. A commonly inherited CVD called Hypertrophic cardiomyopathy (HCM) is defined by an increase in ventricular wall thickness. Little is known about the molecular pathogenesis of HCM apart from its link to mutations in genes encoding sarcomere proteins, including α-cardiac actin (ACTC). My research focuses on the F90Δ and H88Y ACTC variants in early-onset HCM. Studies have shown that myosin activity is largely unchanged with these ACTC variants. I hypothesized that these ACTC variants adversely affect tropomyosin (Tm) regulation, decreasing contractility. Regulated thin filaments (RTFs), and both myosin ATPase assay and an in vitro motility assays were used to generate pCa50 curves. The RTF calcium sensitivity is affected by F90Δ and H88Y variants. These data will contribute to understanding the molecular pathogenesis of early-onset HCM leading to more specialized treatments.
URI: http://hdl.handle.net/10214/14728
Date: 2018-12


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