QUANTITATIVE PROFILING OF OXYLIPINS IN PATIENTS PRESENTING WITH ST ELEVATION MYOCARDIAL INFARCTION (STEMI)

Abstract

Previous studies have shown that there is persistent oxidative stress after myocardial infarction (MI) and percutaneous coronary intervention (PCI). Oxylipins are lipid oxidation products that can be generated mainly by enzymatic oxidation through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP P450) pathways. The aim of this study was to profiling oxylipins before and in various time points after PCI in STEMI patients. Blood samples were collected from subjects with STEMI (n=17) at five time points including prior to PCI (time point 1), and 2h (time point 2), 24h (time point 3), 48h (time point 4) and 30 day (time point 5) following PCI. As controls, blood samples were also collected from subjects (n=20) with non-obstructive coronary artery disease after diagnostic angiography. Oxylipins identification and quantification were performed using high-performance electrospray mass spectrometry and dueterated internal standards. Seventy six oxylipins were identified in STEMI patients which were derived from LOX and CYP pathways and non-enzymatic oxidation. No COX derived oxylipins were identified in patients. The average levels of total oxylipins were 0.08 ± 0.04 and 0.05±0.02 ng/ul of plasma of STEMI patients and controls, respectively. Oxylipins that derived from arachidonic acid (AA) were the most abundant oxylipins in STEMI patients which constituted about 60% of all identified/quantified oxylipins. Oxylipins derived from linoleic acid (LA) were the second most abundant oxylipins which accounted for 28% of all identified/quantified oxylipins in STEMI patients. 20-carboxy-arachidonic acid (20-COOH-AA), which is a metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE) and derived from AA, along with 9-HODE and 12- HODE, which derived from LA, were three most abundant oxylipins in all STEMI groups. One way ANOVA analysis showed that the levels of oxylipins derived from LOX pathway decreased significantly at 24h and 48h after PCI (time point-3 and 4) compared with pre and post PCI (Time point-1, 2). Further analysis revealed that 5-HETE and 9-HODE, were the two LOX derived oxylipins that decreased significantly in this group of oxylipins (p < 0.05). However, other oxylipins derived from CYP pathway or non-enzematic oxidation did not differ significantly between STEMI groups. At 30 day following PCI, levels of oxylipins slightly increased, although it was not significant. This is the first study to determine the oxylipin profile in STEMI patients. As these compounds have potent cardiovascular activities, our data may guide future therapeutics that aim to modulate oxylipins after MI.