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首页> 外文期刊>Journal of thrombosis and haemostasis: JTH >Microsomal prostaglandin E synthase-1, which is not coupled to a particular cyclooxygenase isoenzyme, is essential for prostaglandin E(2) biosynthesis in vascular smooth muscle cells.
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Microsomal prostaglandin E synthase-1, which is not coupled to a particular cyclooxygenase isoenzyme, is essential for prostaglandin E(2) biosynthesis in vascular smooth muscle cells.

机译：微粒体前列腺素E合酶-1，不与特定的环氧合酶同工酶偶联，是前列腺素E（2）在血管平滑肌细胞中生物合成所必需的。

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Background: Prostaglandin (PG) E(2) induces expression of matrix metalloproteinases and angiogenic factors, thereby contributing to plaque instability. Objective: To study the influence of cyclooxygenase (COX) and PGE synthase (PGES) isoenzyme expression on PGE(2) and PGI(2) biosynthesis in vascular smooth muscle cells (VSMC) in culture. Methods: Cells were treated with human recombinant IL-1beta over different periods of time. Expression of PGI synthase, and COX and PGES isoenzymes was determined by real-time reverse transcriptase polymerase chain reaction and immunoblotting. Biosynthesis of prostanoids from exogenous or endogenous substrate was analyzed by high-performance liquid chromatography or enzyme-immunoassay after incubation of cells with labeled arachidonic acid or thrombin, respectively. Results: Cytosolic PGES and microsomal PGES (mPGES) -1 and -2 were expressed in VSMC. PGES activity was mainly linked to mPGES-1. IL-1beta induced COX-2 and mPGES-1 with a different time course. VSMC ability to synthesize PGE(2) and PGI(2) fitted mPGES-1 and COX-2 expression, respectively. The ability of VSMC to produce PGI(2) was downregulated by mPGES-1 expression and was restored when mPGES-1 expression was silenced. Results from COX-1 and COX-2 silencing and selective inhibition showed that both COX-1 and COX-2 were involved in the biosynthesis of PGE(2) and their relative contribution depended on the time of incubation with IL-1beta. Conclusions: mPGES-1 is the main PGES responsible for PGE(2) biosynthesis by VSMC and its induction downregulates VSMC ability to produce PGI(2.) These results support the concept that under inflammatory conditions VSMC could significantly contribute to plaque instability and that mPGES-1 may be a target for therapeutic intervention in patients with cardiovascular risk.
机译：背景：前列腺素（PG）E（2）诱导基质金属蛋白酶和血管生成因子的表达，从而导致斑块不稳定。目的：研究环氧合酶（COX）和PGE合酶（PGES）同工酶表达对培养的血管平滑肌细胞（VSMC）中PGE（2）和PGI（2）生物合成的影响。方法：在不同的时间段内，用人重组IL-1β处理细胞。通过实时逆转录酶聚合酶链反应和免疫印迹确定PGI合酶，COX和PGES同工酶的表达。在分别用标记的花生四烯酸或凝血酶温育细胞后，通过高效液相色谱法或酶免疫分析法分析外源或内源性底物中前列腺素的生物合成。结果：在VSMC中表达了胞质PGES和微粒体PGES（mPGES）-1和-2。 PGES活性主要与mPGES-1相关。 IL-1beta诱导COX-2和mPGES-1的时程不同。 VSMC合成PGE（2）和PGI（2）的能力分别适合mPGES-1和COX-2表达。 VPG产生PGI（2）的能力被mPGES-1表达下调，而当mPGES-1表达沉默时恢复。 COX-1和COX-2沉默及选择性抑制的结果表明，COX-1和COX-2均参与PGE（2）的生物合成，其相对作用取决于与IL-1beta孵育的时间。结论：mPGES-1是负责VSMC生物合成PGE（2）的主要PGES，其诱导下调了VSMC产生PGI（2）的能力。这些结果支持以下观点：在炎症条件下，VSMC可以显着促进斑块不稳定，而mPGES -1可能是心血管风险患者的治疗干预目标。

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