Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques
Lp-PLA2, a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques
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DOI：
10.1016/j.pharma.2015.09.002
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发表时间：
2016-05-01
影响因子：
1.3
通讯作者：
Bonnefont-Rousselot, D.
中科院分区：
文献类型：
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作者：
Bonnefont-Rousselot, D.
慢性炎症参与动脉粥样硬化斑块发展的各个阶段。在动脉粥样硬化形成的新兴生物标志物中，脂蛋白相关磷脂酶A（2）（Lp-PLA（2）），以前称为PAF-乙酰水解酶（McIntyre等人，2009）水解低密度脂蛋白（LDL）的氧化短链磷脂，从而释放促炎介质（溶血磷脂和氧化脂肪酸）。Lp-PLA（2），由单核细胞/巨噬细胞和T淋巴细胞产生，主要与LDL相关（Gazi等人，2005），主要在动脉粥样硬化斑块的坏死中心和富含巨噬细胞的区域中表达（Kolodgie等人，2006年）。它将具有与动脉粥样硬化斑块易损性相关的心血管（CV）事件的预测作用。在CV风险评估中提出了Lp-PLA（2）的测定，以确保对靶向治疗的中等风险人群进行更好的分层（Davidson et al.，2008年）。其促动脉粥样硬化作用表明，抑制其活性可以确保与降胆固醇药物联合使用时更好地保护血管。然而，Lp-PLA（2）还不是用于日常临床实践的完全验证的标志物，特别是因为使用Lp-PLA（2）的抑制剂（darapladib）的研究（STABILITY Investigators等人，2014; O 'Donoghue等人，2014年）没有显示冠状动脉事件的任何减少。Lp-PLA（2）可能在斑块炎症和发展中具有位点特异性作用（Fenning等人，2015年）。高Lp-PLA（2）活性可以反映对动脉粥样硬化的促炎性应激特征的反应（Marvetet al.，2014年）。本报告旨在阐明Lp-PLA（2）参与动脉粥样硬化的病理生理学，并评估其作为CV事件发生的生物标志物和治疗靶点的意义。(C)2015年，国立药学院。由Elsevier Masson SAS出版。All rights reserved.
A chronic inflammation is involved in various stages of development of the atherosclerotic plaques. Among the emerging biomarkers of atherogenesis, the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), formerly known as PAF-acetylhydrolase (McIntyre et al., 2009), hydrolyses the oxidized short chain phospholipids of low-density lipoproteins (LDL), thereby releasing pro-inflammatory mediators (lysophospholipids and oxidized fatty acids). Lp-PLA(2), produced by monocytes/macrophages and T-lymphocytes, and mainly associated with LDL (Gazi et al., 2005), is predominantly expressed in the necrotic center of the atherosclerotic plaques and in the macrophage-rich areas (Kolodgie et al., 2006). It would have a predictive role of cardiovascular (CV) events in relation to the vulnerability of atherosclerotic plaques. Determination of Lp-PLA(2) has been proposed in the assessment of the CV risk, to ensure a better stratification of populations at intermediate risk for targeted therapy (Davidson et al., 2008). Its proatherogenic role suggested that inhibition of its activity could ensure a better vascular protection in combination with cholesterol-lowering agents. Nevertheless, Lp-PLA(2) is not yet a fully validated marker for use in daily clinical practice, especially since the studies using an inhibitor of Lp-PLA(2) (darapladib) (STABILITY Investigators et al., 2014; O'Donoghue et al., 2014) did not show any reduction in coronary events. Lp-PLA(2) could have a site-specific role in plaque inflammation and development (Fenning et al., 2015). High Lp-PLA(2) activity could reflect a response to pro-inflammatory stress characteristic of atherosclerosis (Marathe et al., 2014). This presentation aims at clarifying the involvement of Lp-PLA(2) in the pathophysiology of atherosclerosis, and at assessing its interest both as a biomarker for the onset of CV events and as a therapeutic target. (C) 2015 Academie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.