A Non-Targeted Liquid Chromatographic-Mass Spectrometric Metabolomics Approach for Association with Coronary Artery Disease: An Identification of Biomarkers for Depiction of Underlying Biological Mechanisms.

BACKGROUND We performed non-targeted metabolomics analysis using liquid chromatography-mass spectrometry coupled technique to explore the biological mechanism of coronary artery disease (CAD) events for improved prediction. MATERIAL AND METHODS We studied the association of CAD events in 4092 individuals and observed the replication of sphingomyelin (28:1), lysophosphatidylcholine (18:2), lysophosphatidylcholine (18:1), and monoglyceride (18:2), which were independent of main CAD risk factors. RESULTS We found that these 4 metabolites were responsible for traditional risk factors and also contributed to the modifications related to reclassification and discrimination. Monoglycerides (MonoGs) were positively associated with C-reactive proteins and body mass index, while lysophosphatidylcholines (LPPCs), which had less evidence of subclinical CAD in an additional 1010 participants, yielded a reverse pattern. An association between monoGs and CAD independence of triglycerides (triGs) were also observed. On the basis of Mendelian randomization analysis, we observed a positive but weak irregular effect (odds ratio per unit increase in standard deviation in monoG=1.11, P-value=0.05) on CAD. CONCLUSIONS Our work establishes the relationship of metabolome with coronary artery disease and explains the biological mechanism of CAD events, as we identified the above-mentioned metabolites along with the evidence supporting their clinical use.

Cardioprotective effect of indirubin in experimentally induced myocardial infarction in wistar rats.

Recently, there has been as enhanced interest on global level to recognize the potent antioxidant compounds which are pharmacologically active with less or no side effects. Thus, the current investigation was intended to scrutinize the protective effect of indirubin on the cardiac marker, such as, enzymes, LDH isoenzyme, cardiac troponin-T (cTnT), antioxidant enzymes marker and lipid peroxidation (LPO) in response of isoproterenol (ISO)-induced myocardial infarction (MI) in Wistar rats. The experimental animals were categorized into following groups: Group I received saline; Group II received Indirubin (10 mg/kg); Group III received ISO (100 mg/kg) and Group IV received ISO + indirubin (10 mg/kg) for continuous 10 days. The ISO induced MI injury was confirmed via enhanced level of enzymes markers viz., creatine kinase-MB, creatine kinase, lactate dehydrogensae, troponin-T, alanine transaminase (ALT) and aspartate transaminase (AST) in the rats serum. The enhanced expression of LDH (1 and 2) isoenzyme bands were also observed in the ISO induced MI rats. We have also estimated the level of LPO in the heart and plasma, which was found to be significantly (P<0.05) improved. Moreover, the marker of enzymatic antioxidant enzymes viz., glutathione reductase (GRx), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the heart, and the level of non-enzymatic antioxidant marker viz., vitamin (C, E) in heart and serum were found to be considerably (P<0.05) reduced in the ISO induced MI in Wistar rats. Whereas, the ISO control Wistar rats showed significant (P<0.05) increase in the uric acid level in the plasma. The Indirubin treated rats confirmed the significant protective effect via modulation of all biological and antioxidant parameters tested. The result of the investigation was further found in agreement of the histopathological studies of the indirubin treated rats which clearly showed recovery from the myocardial infarction. Thus, on the basis of that, it has been suggested that indirubin showed protection of myocardial tissues against the ISO persuaded oxidative stress.