Explore the Protective Role of Obesity in the Progression of Myocardial Infarction

Abstract

Obesity has been shown as a risk factor to increase the incidence of myocardial infarction (MI). However, obesity has also been linked to the decreased mortality of acute MI with unknown mechanisms. Here, we firstly used large-scale literature data mining to identify obesity downstream targets and MI upstream regulators with polarity, based on which an obesity-MI regulatory network was constructed. Then, a gene set enrichment analysis was conducted to explore the functional profile of the genes involved in the obesity-MI regulatory networks. After that, a mega-analysis using MI RNA expression datasets was conducted to test the expression of obesity-specific genes in MI patients, followed by a shortest-path analysis to explore any potential gene-MI association. Our results suggested that obesity could inhibit 11 MI promoters, including NPPB, NPPA, IRS1, SMAD3, MIR155, ADRB1, AVP, MAPK14, MC3R, ROCK1, and COL3A1, which were mainly involved in blood pressure-related pathways. Our study suggested that obesity could influence MI progression by driving multiple genes associated with blood pressure regulation. Moreover, PTH could be a novel obesity driven gene associated with the pathogenesis of MI, which needs further validation.