Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids

作     者：Mohamed Al-Shabrawey Ahmed Elmarakby Yara Samra Mohamed Moustafa Stephen WLooney Krishna Rao Maddipati Amany Tawfik 

作者机构：Department of Foundational Medical Studies and Eye Research CenterOakland University William Beaumont School of MedicineRochesterMichiganUSA Eye Research InstituteOakland UniversityRochesterMichiganUSA Department of Oral Biology and Diagnostic SciencesDental College of GeorgiaAugusta UniversityAugustaGeorgiaUSA Departments of Pharmacology&ToxicologyFaculty of PharmacyMansoura UniversityMansouraEgypt Department of BiochemistryFaculty of PharmacyMansoura UniversityEgypt Department of Population Health SciencesMedical College of GeorgiaAugusta UniversityAugustaGeorgiaUSA Bioactive Lipids Research ProgramDepartment of PathologyWayne State UniversityMichiganUSA 

出 版 物：《Life Research》 (TMR生命研究)

年 卷 期：2022年第5卷第2期

页      面：32-41页

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：supported by1R01EY030054(MA),NIH-1R01EY029751(AT) supported in part by National Center for Research Resources,National Institutes of Health Grant S10RR027926 

主　　题：homocysteine cystathionine β-synthase eicosanoids cycloxygenase lipoxygenase cytochrome-P450 

摘      要：Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal *** cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/*** 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)*** control ***-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT *** acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control ***(COX)metabolites were also significantly decreased in cβs^(+/-)*** control *** data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic *** increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs *** of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.