Extracellular Matrix Proteins Changes in the Left Ventricular Unloading and Overloading after Myocardial Infarction

Abstract

AbstractBackgroundThe cardiac extracellular matrix (ECM) is a dynamic scaffold that transmits and responds to forces that act on the heart during the cardiac cycle. While acute left ventricle (LV) unloading by percutaneous LV assist device (pLVAD) is now a therapeutic option, its impact on ECM is unknown. We hypothesize that the composition of LV ECM proteins changes in response to reduced wall stress with mechanical LV unloading.MethodsTen Yorkshire pigs underwent myocardial infarction, and one week later were subjected to either 2 hours of LV unloading with pLVAD or 2 hours of LV overloading by mechanically-induced acute aortic regurgitation. Non-ischemic remote myocardium was processed for ECM specific proteomics. Volcano plots were constructed to determine differentially expressed proteins between the groups. Gene ontology (GO) analysis was performed to identify associated molecular processes and biological functions. Immunofluorescence microscopy was performed to validate differential protein expression.ResultsOf the 986 proteins analyzed, 39 were significantly differentially expressed between overloaded and unloaded myocardium. GO analysis by molecular function revealed that differences tending towards RNA binding and lipid binding proteins. Analysis by biological process showed that cell differentiation, vesicle transport, and programmed cell death were the processes most affected. Staining for three of the identified differentially expressed proteins had results congruent with proteomic analysis.ConclusionsThere were significant differences in the protein composition of the cardiac ECM between acutely unloaded and overloaded myocardium, suggesting that it actively responds to altered LV load.