Beyond Lipoprotein(a) plasma measurements: Lipoprotein(a) and inflammation.
Beyond Lipoprotein(a) plasma measurements: Lipoprotein(a) and inflammation.
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DOI：
10.1016/j.phrs.2021.105689
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发表时间：
2021-07
影响因子：
9.3
通讯作者：
Westerterp, Marit
中科院分区：
文献类型：
--
作者：
Reyes-Soffer, Gissette;Westerterp, Marit
全基因组关联、流行病学和临床研究已经确定高脂蛋白(a) [Lp(a)]是动脉粥样硬化性心血管疾病（ASCVD）的因果危险因素。Lp(a)是一种载脂蛋白ob100，含有与载脂蛋白(a) [apo(a)]（一种糖蛋白）共价结合的脂蛋白。血浆Lp(a)水平在很大程度上由遗传决定。其与心血管疾病（CVD）的联系可能是由其促炎作用驱动的，其中与Lp(a)结合的氧化磷脂（oxPL）的关联研究最多。各种炎症状况，如类风湿关节炎（RA）、系统性红斑狼疮、获得性免疫缺陷综合征和慢性肾衰竭都与高Lp(a)水平有关。在RA病例中，高Lp(a)水平可通过托珠单抗阻断白细胞介素-6受体（IL-6R）逆转，提示IL-6在调节Lp(a)血浆水平中的潜在作用。IL-6和IL-6R多态性水平升高与心血管疾病有关。旨在降低载脂蛋白(a)从而降低血浆Lp(a)水平的疗法正在临床试验中。他们的研究结果将决定载脂蛋白(a)和脂蛋白(a)的降低是否会降低心血管疾病的预后。当我们进入这个新的可用治疗领域时，有必要提高我们对机制的理解。本文将重点讨论Lp(a)在炎症和心血管疾病中的作用。
Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is an apoB100 containing lipoprotein covalently bound to apolipoprotein(a) [apo(a)], a glycoprotein. Plasma Lp(a) levels are to a large extent determined by genetics. Its link to cardiovascular disease (CVD) may be driven by its pro-inflammatory effects, of which its association with oxidized phospholipids (oxPL) bound to Lp(a) is the most studied. Various inflammatory conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus, acquired immunodeficiency syndrome, and chronic renal failure are associated with high Lp(a) levels. In cases of RA, high Lp(a) levels are reversed by interleukin-6 receptor (IL-6R) blockade by tocilizumab, suggesting a potential role for IL-6 in regulating Lp(a) plasma levels. Elevated levels of IL-6 and IL-6R polymorphisms are associated with CVD. Therapies aimed at lowering apo(a) and thereby reducing plasma Lp(a) levels are in clinical trials. Their results will determine if reductions in apo(a) and Lp(a) decrease cardiovascular outcomes. As we enter this new arena of available treatments, there is a need to improve our understanding of mechanisms. This review will focus on the role of Lp(a) in inflammation and CVD.
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