Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms.
Sex differences in specialized pro-resolving lipid mediators and their receptors in abdominal aortic aneurysms.
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DOI：
10.1016/j.jvssci.2023.100107
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Upchurch, Gilbert R Jr
中科院分区：
文献类型：
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作者：
Filiberto, Amanda C;Leroy, Victoria;Ladd, Zachary;Su, Gang;Elder, Craig T;Pruitt, Eric Y;Lu, Guanyi;Hartman, Joseph;Zarrinpar, Ali;Garrett, Timothy J;Sharma, Ashish K;Upchurch, Gilbert R Jr
在这项研究中，我们测试了一个假设，即内源性表达的专门促消退脂质介质（SPM），促进炎症的解决，特别是Resolvin D1和-D2，以及Maresin 1（MaR 1），可以影响腹主动脉瘤（AAA）的形成和进展，在性别特异性的方式。SPM表达定量主动脉组织从人AAA样品和从小鼠体内AAA模型通过液相色谱-串联质谱。SPM受体FPR 2、LGR 6和GPR 18的mRNA表达通过实时聚合酶链反应进行定量。采用Student t检验和非参数Mann-Whitney或Wilcoxon检验进行组间配对比较。采用事后Tukey检验后的单因素方差分析确定多个比较组之间的差异。人主动脉组织分析显示，与对照组相比，男性AAA中RvD 1水平显著降低，而与男性对照组相比，男性AAA中FPR 2和LGR 6受体表达下调。弹性蛋白酶处理小鼠的体内研究显示，与雌性相比，雄性小鼠的主动脉组织中RvD 2和MaR 1以及SPM前体、ω-3脂肪酸DHA和EPA的水平更高。与雄性相比，弹性蛋白酶处理的雌性中FPR 2表达增加。我们的研究结果表明，特定的差异SPM及其相关的G-蛋白偶联受体之间存在性别。这些结果表明SPM介导的信号通路在影响AAAs发病机制的性别差异中的相关性。AAA是一个严重的临床问题，可导致主动脉突然破裂和死亡。最近的研究表明，性别差异在AAA形成过程中起着关键作用，因为女性主动脉瘤疾病的发病率较低，但干预后的结局似乎更差。很少有研究探讨这些差异背后的潜在原因。在这项研究中，我们测试的假设，内源性SPM的表达及其受体的性别差异存在于男性和女性之间，这种差异可能与AAA的形成。
In this study, we tested the hypothesis that endogenous expression of specialized pro-resolving lipid mediators (SPMs) that facilitate the resolution of inflammation, specifically Resolvin D1and -D2, as well as Maresin1 (MaR1), can impact abdominal aortic aneurysm (AAA) formation and progression in a sex-specific manner. SPM expression was quantified in aortic tissue from human AAA samples and from a murine in vivo AAA model via liquid chromatography-tandem mass spectrometry. mRNA expression for SPM receptors FPR2, LGR6, and GPR18 were quantified by real-time polymerase chain reaction. A Student t test with nonparametric Mann-Whitney or Wilcoxon test was used for pair-wise comparisons of groups. One-way analysis of variance after post hoc Tukey test was used to determine the differences among multiple comparative groups. Human aortic tissue analysis revealed a significant decrease in RvD1 levels in male AAAs compared with controls, whereas FPR2 and LGR6 receptor expressions were downregulated in male AAAs compared with male controls. In vivo studies of elastase-treated mice showed higher levels of RvD2 and MaR1 as well as the SPM precursors, omega-3 fatty acids DHA and EPA, in aortic tissue from males compared with females. FPR2 expression was increased in elastase-treated females compared with males. Our findings demonstrate that specific differences in SPMs and their associated G-protein coupled receptors exist between sexes. These results indicate the relevance of SPM-mediated signaling pathways in sex differences impacting the pathogenesis of AAAs. AAAs are a substantial clinical problem and can lead to sudden aortic rupture and death. Recent studies have shown a critical role for sex disparity during AAA formation, as female sex has a lower incidence of aortic aneurysm disease, but their outcomes following intervention appear to be worse. Few studies have examined the potential causes that underlie these differences. In this study, we tested the hypothesis that sex differences in endogenous SPM expression and their receptors exist between males and females and that this difference could be associated with AAA formation.