PDF(Pubmed)
Abstract：
Arachidonic acid (AA) metabolites have been associated with several diseases across various organ systems, including the cardiovascular, pulmonary, and renal systems. Lipid mediators generated from AA oxidation have been studied to control macrophages, T-cells, cytokines, and fibroblasts, and regulate inflammatory mediators that induce vascular remodeling and dysfunction. AA is metabolized by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) to generate anti-inflammatory, pro-inflammatory, and pro-resolutory oxidized lipids. As comorbid states such as diabetes, hypertension, and obesity become more prevalent in cardiovascular disease, studying the expression of AA pathway genes and their association with these diseases can provide unique pathophysiological insights. In addition, the AA pathway of oxidized lipids exhibits diverse functions across different organ systems, where a lipid can be both anti-inflammatory and pro-inflammatory depending on the location of metabolic activity. Therefore, we aimed to characterize the gene expression of these lipid enzymes and receptors throughout multi-organ diseases via a transcriptomic meta-analysis using the Gene Expression Omnibus (GEO) Database. In our study, we found that distinct AA pathways were expressed in various comorbid conditions, especially those with prominent inflammatory risk factors. Comorbidities, such as hypertension, diabetes, and obesity appeared to contribute to elevated expression of pro-inflammatory lipid mediator genes. Our results demonstrate that expression of inflammatory AA pathway genes may potentiate and attenuate disease; therefore, we suggest further exploration of these pathways as therapeutic targets to improve outcomes.
摘要：
花生四烯酸（AA）代谢产物与各种器官系统中的几种疾病有关。包括心血管疾病,肺,和肾脏系统。已经研究了由AA氧化产生的脂质介质来控制巨噬细胞，T细胞,细胞因子,和成纤维细胞，并调节诱导血管重塑和功能障碍的炎症介质。AA被环氧合酶（COX）代谢，脂氧合酶（LOX），和细胞色素P450（CYP）产生抗炎，促炎,和可分离的氧化脂质。如糖尿病等合并症，高血压,肥胖在心血管疾病中变得更加普遍，研究AA通路基因的表达及其与这些疾病的关联可以提供独特的病理生理学见解。此外,氧化脂质的AA途径在不同的器官系统中表现出不同的功能，其中脂质可以是抗炎和促炎的，这取决于代谢活性的位置。因此,我们的目的是通过使用基因表达综合(GEO)数据库的转录组荟萃分析来表征这些脂质酶和受体在整个多器官疾病中的基因表达。在我们的研究中,我们发现不同的AA途径在各种共病条件下表达，尤其是那些具有突出炎症危险因素的患者。合并症,比如高血压，糖尿病,肥胖似乎有助于促炎脂质介质基因的表达升高。我们的结果表明，炎性AA途径基因的表达可能增强和减轻疾病；因此，我们建议进一步探索这些途径作为改善结局的治疗靶点.
