Serum lipid feature and potential biomarkers of lethal ventricular tachyarrhythmia (LVTA) induced by myocardial ion channel diseases: a rat model study
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To determine the cause of death in myocardial ion channel diseases (MICD)-induced sudden cardiac death (SCD) cases is a difficulty in forensic identification practices. The majority of MICD-induced SCD cases would experience lethal ventricular tachyarrhythmia (LVTA) before deaths; thus, confirming the occurrence of LVTA in bodies can offer a key evidence to identify these cases. Several lipids in the myocardia were found disturbed after LVTA; yet, whether serum lipidome would be disrupted by LVTA is not clear. Therefore, we aimed to screen lipid feature and related diagnostic markers of LVTA in serum here. An aconitine-induced LVTA-SCD rat model was produced. Blood samples before LVTA and immediately after LVTA were retrieved and related serum specimens were used for ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics analyses. On the basis of the defined differential lipids, a lipid-related metabolic pathway network was constructed and potential biomarkers were screened. Twelve aconitine-induced LVTA rats were produced. Totally, 188 lipids in serum were disrupted during the LVTA-SCD process, which belong to 11 lipid classes. Most of the differential lipids were correlated, suggesting that they were interacted and that the changes were holistic during LVTA process. Ten lipid pathways were activated during LVTA process; the main lipid classes involved in these pathways were ceramide, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Phosphatidylcholine O-40:4, sphingomyelin d46:5, and phosphatidylethanolamine 40:4 were tested as potential diagnostic markers of LVTA-SCD event in serum. The current results indicate a substantial change in serum lipidome after LVTA-SCD; lipidomics holds promise to identify MICD-induced SCDs in forensic practices.
KeywordsMyocardial ion channel diseases Sudden cardiac death Lethal ventricular tachyarrhythmia Lipidomics Diagnostic markers
This work was supported by grants from the Natural Science Foundation (2015A408119346049), the Science and Technology Innovation project (2013KJCX0076) of Guangdong Province, and the Natural Science Foundation of Shanghai (15ZR1430300), China.
Compliance with ethical standards
This study was approved by the Medical Animal Care and Welfare Committee at Shantou University Medical College (number of authorization: SUMC 2014-157). All procedures were carried out in accordance with the Guide for Care and Use of Laboratory Animals of our College.
Conflict of interest
The authors declare that they have no conflict of interest.
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