Abstract 316: Cell-Matrix Contacts Regulate Age-Associated Cardiac Function

Abstract

An increased deposition of ECM is observed in all advanced age heart failure patients. Therefore, it is necessary to investigate the effect of extracellular remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms such as Drosophila melanogaster . The bilayered design of the Drosophila heart-tube makes it an easier model in which to study the interplay between ECM and cardiomyocytes as they regulate contraction. Here we present data from two common wildtype strains of Drosophila exhibiting different aging profiles in terms of cytoskeletal and ECM regulation and remodeling. Using a recently developed nanoindentation method to measure cardiomyocyte stiffness of intact Drosophila hearts, we have found that while yellow-white ( yw ) flies show midline stiffening at the intercalated discs (ICD) presenting a clear diastolic dysfunction with age, the white-1118 ( w1118 ) flies exhibit no ICD stiffening, but show an increase in thickness of the ECM layer between the ventral muscle (VM) and cardiomyocytes (CM). Paired with increased expression of ECM proteins, the w1118 Drosophila line may provide a good model for exploring the effect of cell-ECM contacts on regulating cardiac function with age. Knock-down of integral ECM genes LamininA and Viking (Collagen IV) result in no effect on cardiac performance in juvenile flies but causes a decrease in underlying cardiomyocyte stiffness and an increase in the contractile irregularity of heart beats. This suggests that the cell-ECM contacts in the basement membrane are intimately tied to coupling of the cardiomyocytes of the Drosophila heart-tube, which may have larger implications for elderly patients suffering from myocardial fibrosis and experiencing cardiomyocyte decoupling and resultant arrhythmias.