The molecular mechanism of ischemic myocardial injury is still a hot topic in the international academic circles. In this paper, C57BL/6 wild type (WT) mouse strains, very low density lipoprotein (VLDL) receptor knockout (VLDLR-KO) mice and VLDL receptor transgenic (VLDLR-TG) mice, were selected to investigate on the effect of VLDL receptor on myocardial ischemic injury in vivo and in vitro. Key molecular signaling pathways were found based on the biomolecular network analyses. A causal relationship between VLDL receptor→MAPKs, AKT, NF-κB signaling pathway and the pathological phenotype of myocardial infarction, was identified by computational analysis of functional modules across biological networks, to illustrate the effect of VLDL receptor molecular mechanism in myocardial ischemic injury.