冠状动脉性心脏病(coronary artery disease, CAD)显著影响着我国居民的健康,也给全球医疗带来巨大的经济负担。动脉粥样硬化(atherosclerosis, AS)是CAD的病理基础。胆固醇-25-羟化酶(cholesterol 25-hydroxylase, CH25H)是一种参与脂质代谢的酶,它可以将胆固醇催化生成25-羟基胆固醇(25-hydroxycholesterol, 25-HC),而25-HC是众所周知的胆固醇的氧化产物,即氧甾醇。既往的研究表明CH25H和25-HC在调节胆固醇的代谢、炎症反应、AS以及免疫反应和抗病毒感染等方面发挥多种作用。近年来越来越多的研究聚焦于CH25H和25-HC与AS和CAD的相关性。因此本文就CH25H和25-HC在AS和CAD中已知的作用机制简单作一综述。Coronary artery disease (CAD) significantly affects the health of Chinese residents and imposes a huge economic burden on global healthcare. Atherosclerosis (AS) is the pathological basis of CAD. Cholesterol 25 hydroxylase (CH25H) is an enzyme involved in lipid metabolism. It catalyzes the conversion of cholesterol into 25-hydroxycholesterol (25-HC), which is a well-known oxidation product of cholesterol. Previous studies have shown that CH25H and 25-HC play multiple roles in regulating cholesterol metabolism, inflammatory response, AS, immune response, and antiviral infection. In recent years, more and more research has focused on the correlation between CH25H and 25-HC with AS and CAD. Therefore, this article provides a brief overview of the known mechanisms of action of CH25H and 25-HC in AS and CAD.
目的:探讨精氨酸酶1 (arginase 1, ARG1)在冠状动脉性心脏病(coronary heart disease, CHD)中的转录表达水平及潜在致病机理。方法:整合CHD相关多中心高通量数据,计算ARG1 mRNA表达水平标准化平均差(standardized mean difference, SMD),通过汇总受试者工作特征曲线,灵敏度,特异度,似然比等指标来评价ARG1在CHD中的临床病理意义。利用孟德尔随机化法确定ARG1和CHD之间的因果联系,最后通过京都基因与基因组百科全书以及蛋白质–蛋白质相互作用分析明确ARG1在CHD中的潜在调控机制。结果:本研究共纳入6个平台14个CHD数据集,含427例CHD样本,296例正常对照样本。ARG1表达在CHD中显著上调,其标准化平均差为0.44 (95% CI: 0.06~0.83),汇总受试者工作特征曲线下面积为0.72 (95% CI: 0.68~0.76),灵敏度为0.55 (95% CI: 0.36~0.73),特异度为0.79 (95% CI: 0.55~0.92),阳性似然比为2.61 (95% CI: 1.16~5.86)、阴性似然比为0.57 (95% CI: 0.38~0.85);孟德尔随机化法未见ARG1与CHD之间的显著关联(OR = 0.9833, 95% CI = 0.9408~1.0278, p = 0.4563);ARG1可通过部分信号通路影响CHD的进展,如利什曼病、中性粒细胞胞外陷阱的形成、癌症中PD-L1表达和PD-1检查点等通路。结论:ARG1可能作为促进CHD发生的关键基因参与疾病的发生发展。Objective: To investigate the transcriptional expression levels of arginase 1 (ARG1) in coronary heart disease (CHD) and its potential pathogenic mechanisms. Methods: Integrating multi-center high-throughput data related to CHD, we computed the standardized mean difference (SMD) of ARG1 mRNA expression levels. The clinical pathological significance of ARG1 in CHD was evaluated through aggregated receiver operating characteristic curves, sensitivity, specificity, and likelihood ratios. Mendelian randomization was employed to determine the causal relationship between ARG1 and CHD. The potential regulatory mechanisms of ARG1 in CHD were clarified through the Kyoto Encyclopedia of Ge
