Synthesis Of OEA Analogues And Study Of The Influence Of Analogues Induced Expression Of PPARa In HUVECs

Background: Atherosclerosis(AS), the principal cause of heart attack, stroke andgangrene of the extremities, accounts for 50% of mortality in the USA, Europe andJapan. The American Heart Association estimates that cardiovascular diseases affect57 million Americans, and each year cause 954,000 deaths and cost 259 billiondollars.Oleoylethanolamide (OEA) is an endogenous lipid that modulates feeding, bodyweight and lipid metabolism by binding with high affinity to the ligand-activatedtranscription factor, peroxisome proliferator-activated receptor-alpha (PPARα).PPARα. has been implicated in variety of metabolic processes, it is expressed inavariety of tissues, but most prominently in liver, heart, kidney, muscle and brownadipose tissue. OEA is a natural ligand for PPARa with a half-maximal concentration(EC₅₀)of 120nM.To study the structural selectivity of PPARa activation, we have synthesizedseveral OEA analogues.Object: To observe the influence of OEA analogues induced expression of PPARa inhuman umbilical vein endothelial cells(HUVECs) and to investigate the relationbetween the structure and the effect, we hope to find better medicine.Methods: The experiment includes two stages: First, we have synthesized severalOEA analogues. Second, the expression of PPARa in mRNA level was deteced withreverse transcription polymerase chain reaction( RT-PCR).Results: The methyl derivative of OEA can increase the expression of PPARα-mRNAin HUVECs, and the effect is stronger than OEA; While the compounds ofepoxidation and cyclopropanation do not significantly activate PPARα.Conclusion: When OEA analogues binding to PPARα-LBD, the double bond and theethanolamide moiety play an important role. When designing midicine later, weshould only change the ethanolamide moiety and reserve the double bond. chain reaction...