Integrative analyses of myocardial lipidome and proteome implicate mitochondrial dysfunction in lethal ventricular tachyarrhythmia (LVTA) induced by acute myocardial ischemia (AMI)

Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological event leading to sudden cardiac death (SCD). In this study, the myocardial lipidome and proteome were analysed in rats experiencing LVTA as a consequence of acute myocardial ischemia (AMI). Results showed that 257 lipid species and 814 myocardial proteins were disrupted during LVTA. Cardiolipin (CL), phosphatidylcholine (PC), phosphatidylethanolamine (PE), ceramide (Cer), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC), phosphatidylglycerol (PG), and lysophosphatidylserine (LPS) were down-regulated; whereas sphingosine (SO) and diacylglycerol (DG) were up-regulated. Enrichment analysis of these proteins suggested mitochondrial dysfunction. Most of the differential lipids showed a high degree of interaction with the core differentially expressed proteins. Seven lipid pathways, including DG → PE, PE → LPE, PA → DG, PC → DG, PE → PA, Cer → SM, and LPE → LPC, were active during the process. Activation of LPE → PE could be partially confirmed by proteomic results. CL (72:7), PE (42:4), and LPE (P-18:0) jointly represent a promising diagnostic markers for LVTA. Collectively, we discovered marked disturbances of the lipidome and proteome in the myocardia of LVTA rats, mainly involving dysfunction of the mitochondrial respiratory chain.