| Background: Acute myocardial infarction(AMI)commonly known as a heart attack,occurs when blood stops flowing properly to a part of the heart,and the heart muscle is injured.In China,AMI is becoming a more common cause of death.?-3 polyunsaturated fatty acids(PUFAs)was reported to play protective roles in cardiovascular diseases,which can be metabolized to hundreds of eicosanoids by sets of enzymes in three pathways,named cyclooxygenase(COX),lipoxygenase(LOX),cytochrome(CYP)450.However,the mechanism is poorly understood.Therefore,the study as to the metabolic pathways and products of PUFAs is vital to understand the cardiac-protective function.Aims: This study is to investigate the abnormal changes of PUFAs metabolic profile and its relationship with AMI using metabolomics methods.Meanwhile,patients with AMI were randomly assigned to receive ?-3 PUFAs plus regular treatment or regular treatment alone.Cardiac function,endothelial function and plasma inflammatory cytokines were assessed just before and after 12 weeks of treatment in both groups.The changes of metabolic pathways and corresponding metabolites of PUFAs were also detected in order to explore protective mechanism of ?-3 PUFAs.Methods: 1.Twenty patients with AMI were enrolled in this study and another twenty patients with normal coronary angiography served as controls.The PUFAs profiles in both groups were detected by ultra-performance liquid chromatography tandem mass spectrometry.2.Sixty AMI patients with successful percutaneous coronary intervention(PCI)were recruited into the study and randomized to the ?-3 group(n=30;standard therapy + ?-3 PUFAs 2 g dialy)or the control group(n=30;standard therapy).Echocardiography,endothelial function,blood fats,serum cytokines levels and PUFAs profile were obtained before and after 4 and 12 weeks.Results:1.In group AMI,we found that 6k-PGF1? via ARA-COX pathway was decreased;PGF2?,PGJ2 were increased.12-HETE,15-HETE,15-oxo-ETE,5-HETE,8-HETE,LTB4 via ARA-LOX pathway and 11,12-/14,15-/5,6-/8,9-DHET,19-HETE via ARA-CYP450 pathway were increased.10 S,17S-Di HDo HE,20-Hdo HE via DHA-LOX pathway were decreased;while 14-HDo HE,Rv D1 were increased.PGA3/B3/F3?,5-HEPE and 5,6-Di HETE via EPA-COX,LOX and CYP450 pathway respectively were increased.The productions of LA exhibited elevated levels.Correlation analysis between productions of PUFAs and AMI was calculated.We found a negative correlation between AMI and 15d-PGJ2,6k-PGF1?,and a positive correlation between PGF2?,12-/15-/5-/8-HETE,15-oxo-ETE,LTB4,Rv D1,PGA/B3,5,6-Di HETE,14,15-/5,6-/8,9-DHET,13-/9-HODE,12,13-/9,10-Ep OME and AMI.Moreover,the correlationship among these productions was also carried out,and PGF2? showed the highest correlation with others.2.After treatment for 12 weeks,both groups showed decrease in TCHO,LDL-c,hs-CRP.In ?-3 group,serum NO significantly increased,while Apo B and Lp(a)decreased.However,there were no differences in MACE,LVEF,LVSD,ADMA,FMD,IMT,blood pressure and heart rate between the two groups.11-HETE,15-HETE,5-HETE via ARA-LOX pathway and EETs,EEQs via CYP450 pathway were declined,whereas Maresin via DHA-LOX pathway was rose in control group after therapy.6k-PGF1? via ARA-COX pathway showed an improvement in ?-3 group 12 weeks later,and PGF2?,PGJ2,LTB4 decreased.Correlation analysis between NO level and productions of PUFAs was calculated.There was a positive correlation between DHA,6k-PGF1? and elevated level of serum NO,while a negative correlation between PGJ2 and NO.Conclusion: There are differences in PUFAs metabolic profile between AMI patients and health people,and the metabolism of ARA was active in AMI patients.Both conventional treatment and supplementation of omega-3 PUFAs can improve the metabolic profile of PUFAs,especially patients will benefit from ?-3 PUFAs by maintaining a balance between 6k-PGF1? and PGF2?,PGJ2,LTB4. |
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