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首页> 外文期刊>Current opinion in lipidology >The roles of PON1 and PON2 in cardiovascular disease and innate immunity.
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The roles of PON1 and PON2 in cardiovascular disease and innate immunity.

机译：PON1和PON2在心血管疾病和先天免疫中的作用。

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PURPOSE OF REVIEW: The paraoxonase (PON) gene family includes three members, PON1, PON2, and PON3. In-vitro and mouse studies have demonstrated that all three PONs are atheroprotective. Some, but not all, human epidemiologic studies have observed associations between PON gene polymorphisms and risk of cardiovascular disease (CVD). In this review, we summarize studies published within the last year, elucidating involvement of PON1 and PON2 in oxidative stress, CVD, and innate immune responses. RECENT FINDINGS: In a prospective study, the PON1 192QQ genotype and low PON1 activity were associated with increased systemic oxidative stress and increased risk for CVD. PON1 expression protected against Pseudomonas aeruginosa lethality in Drosophila, suggesting that PON1 can interfere with quorum sensing in vivo. PON2 attenuated macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1. Overexpression of PON2 protected against endoplasmic reticulum stress-induced apoptosis when the stress was induced by interference with protein modification but not when endoplasmic reticulum stress was induced by Ca2+ deregulation. SUMMARY: Both mouse and human studies have demonstrated the antioxidative and atheroprotective effects of PON1. The mechanisms by which PON2 exerts its atheroprotective effects are emerging. Large-scale epidemiologic studies are needed to further examine the relationship between PON2 genetic polymorphisms and risk for CVD. Elucidation of the physiologic substrates of the PON proteins is of particular importance to further advance this field.
机译：审查目的：对氧磷酶（PON）基因家族包括三个成员，PON1，PON2和PON3。体外和小鼠研究表明，所有三种PON具有抗动脉粥样硬化作用。一些（但不是全部）人类流行病学研究已经观察到PON基因多态性与心血管疾病（CVD）风险之间的关联。在这篇综述中，我们总结了去年发表的研究，阐明了PON1和PON2参与氧化应激，CVD和先天性免疫反应。最新发现：在一项前瞻性研究中，PON1 192QQ基因型和低PON1活性与全身氧化应激增加和CVD风险增加相关。 PON1表达可防止果蝇中的铜绿假单胞菌致死性，这表明PON1可以干扰体内的群体感应。 PON2通过抑制二酰基甘油酰基转移酶来减弱巨噬细胞甘油三酸酯的积累1.当蛋白2的修饰干扰诱导应激时，PON2的过表达可保护内质网应激诱导的细胞凋亡，而Ca2 +失调诱导内质网应激则不能。摘要：小鼠和人体研究均证明PON1具有抗氧化和抗动脉粥样硬化的作用。 PON2发挥其抗动脉粥样硬化作用的机制正在出现。需要进行大规模的流行病学研究，以进一步检查PON2基因多态性与CVD风险之间的关系。阐明PON蛋白的生理底物对于进一步推进该领域特别重要。

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