Oral 1 - 1.1
1,2Sina Hadipour-Lakmehsari, 3,4,5Amine Driouchi, 1,2Shin-Haw Lee, 1,5Uros Kuzmanov, 1,4Neal I. Callaghan, 1,4Craig A. Simmons, 4,5Chris M. Yip, 1,2Anthony O. Gramolini
1 Ted Rogers Centre for Heart Research, University of Toronto; 2 Dept. of Physiology, University of Toronto; 3 Dept. of Biochemistry, University of Toronto; 4 Institute of Biomaterials and Biomedical Engineering, University of Toronto; 5 Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Heart failure is a debilitating, widespread disease endpoint characterized by weakening of cardiac muscle and a deficit between the metabolic demands of the body and the supply of blood. One of the main manifestations of heart failure is aberrant and disorganized calcium signaling within the cardiomyocyte, resulting in contractile inefficiencies. It has been shown that calcium cycling proteins such as RyR2, SERCA, and PLN undergo biochemical changes during cardiac disease, and eventually, heart failure which alter their function. Our study investigated whether these calcium cycling changes were accompanied by modified organization, localization, and patterns of expression of RyR2, SERCA2a, PLN, and DHPR during disease progression. We used dSTORM super-resolution microscopy to visualize these proteins at nanoscale resolution and to be able to quantify the changes observed via Voronoi tesselation. Our findings show there are widespread changes in the patterns of expression of these proteins as shown by visualization of images as well as quantified cluster analyses. Cluster area, intensity, and density were investigated for each of the proteins. These measurements showed different averages of the values mentioned above, as well as differential distribution curves. frequencies Periodicity analyses and immunoblots demonstrate changes in some of the proteins investigated. Our work demonstrates the adaptations of calcium cycling proteins within the cardiomyocyte upon pressure overload and hypertrophic disease and sheds light on a previously unknown pathogenic mechanism.