Quantitative proteomic changes during post myocardial infarction remodeling reveals altered cardiac metabolism and Desmin aggregation in the infarct region

Myocardial infarction is one of the leading causes of cardiac dysfunction, failure and sudden death. Post infarction cardiac remodeling presents a poor prognosis, with 30%-45% of patients developing heart failure, in a period of 525 years. Oxidative stress has been labelled as the primary causative factor for cardiac damage during infarction, however, the impact it may have during the process of post infarction remodeling has not been well probed. In this study, we have implemented ITRAQ proteomics to catalogue proteins and functional processes, participating both temporally (early and late phases) and spatially (infarct and remote zones), during post myocardial infarction remodeling of the heart as functions of the differential oxidative stress manifest during the remodeling process. Cardiac metabolism was the dominant network to be affected during infarction and the remodeling time points considered in this study. A distinctive expression pattern of cytoskeletal proteins was also observed with increased remodeling time points. Further, it was found that the cytoskeletal protein Desmin, aggregated in the infarct zone during the remodeling process, mediated by the protease Calpain1. Taken together, all of these data in conjunction may lay the foundation to understand the effects of oxidative stress on the remodeling process and elaborate the mechanism behind the compromised cardiac function observed during post myocardial infarction remodeling. Significance: Oxidative stress is the major driving force for cardiac damage during myocardial infarction. However, the impact of oxidative stress on the process of post MI remodeling in conducting the heart towards functional failure has not been well explored. In this study, a spatial and temporal approach was taken to elaborate the major proteins and cellular processes involved in post MI remodeling. Based on level/ intensity of ROS, spatially, infarct and noninfarct zones were chosen for analysis while on the temporal scale, early (30 days) and late time points (120 days) post MI were included in the study. This design enabled us to delineate the differential protein expression on a spectrum of maximum oxidative stress at infarct zone during MI to minimum oxidative stress at noninfarct zone during late time point post MI. The proteome profiles for each of the study groups when comparatively analysed gave a holistic idea about the dominant cellular processes involved in post MI remodeling such as cardiac metabolism, both for short term and long term remodeling as well as unique processes such as Desmin mediated cytoskeletal remodeling of the infarcted myocardium that are involved in the compromise of cardiac function. (C) 2016 Elsevier B.V. All rights reserved.