Recent developments with lipoprotein-associated phospholipase A2 inhibitors.

Chauffe RJ; Wilensky RL; Mohler ER 3rd

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Recent developments with lipoprotein-associated phospholipase A2 inhibitors.

机译：与脂蛋白相关的磷脂酶A2抑制剂的最新进展。

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Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a calcium-independent phospholipase A(2) enzyme secreted by leukocytes and associated with circulating low-density lipoprotein and macrophages in atherosclerotic plaques. Until recently, the biological role of Lp-PLA(2) in atherosclerosis was controversial, but now the preponderance of evidence demonstrates a proatherogenic role of this enzyme. Lp-PLA(2) generates two proinflammatory mediators, lysophosphatidylcholine and oxidized nonesterified fatty acids, which play a major role in the development of atherosclerotic lesions and formation of a necrotic core, leading to more vulnerable plaques. These findings have opened the door to a potential novel therapeutic target, selective inhibition of Lp-LPA(2). Recently, both animal models and human studies have shown that selective inhibition of Lp-PLA(2) reduces plasma Lp-PLA(2) activity, plaque area, and necrotic core area. This article reviews the most recent developments with Lp-PLA(2) inhibitors.

机译：脂蛋白相关的磷脂酶A（2）（Lp-PLA（2））是白细胞分泌的钙依赖性磷脂酶A（2）酶，与动脉粥样硬化斑块中循环的低密度脂蛋白和巨噬细胞相关。直到最近，Lp-PLA（2）在动脉粥样硬化中的生物学作用一直是有争议的，但是现在有大量证据证明了该酶的促动脉粥样硬化作用。 Lp-PLA（2）产生两种促炎性介质，溶血磷脂酰胆碱和氧化的非酯化脂肪酸，它们在动脉粥样硬化病变的发展和坏死核心的形成中起主要作用，导致斑块更脆弱。这些发现为潜在的新型治疗目标，即选择性抑制Lp-LPA（2）打开了大门。最近，动物模型和人体研究均表明，选择性抑制Lp-PLA（2）会降低血浆Lp-PLA（2）活性，噬菌斑面积和坏死核心面积。本文回顾了Lp-PLA（2）抑制剂的最新发展。

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《Current atherosclerosis reports.》 |2010年第1期|共5页
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Chauffe RJ; Wilensky RL; Mohler ER 3rd;
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中图分类心脏、血管（循环系）疾病;
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机译：与脂蛋白相关的磷脂酶A2抑制剂的最新进展。
2. Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA(2)) [J] . Woolford Alison J. -A., Day Philip J., Beneton Veronique, Journal of Medicinal Chemistry . 2016,第23期

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3. Increased plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are related to good collateral development in patients with isolated left coronary artery disease. [J] . Orem C, Kahraman N, Orem A, International Journal of Cardiology . 2011,第1期

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4. Secretory phospholipase A2 and pulmonary surfactant interaction: a vicious circle during the development of acute respiratory distress syndrome. [C] . Acta pharmacologica sinica . 2002

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Recent developments with lipoprotein-associated phospholipase A2 inhibitors.

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