Center of the Study of Chronic Diseases, New University of Lisbon, Lisbon, Portugal.
Medicine 4 Department, Fernando Fonseca Hospital, Amadora, Portugal.
Immunology. 2021 Oct;164(2):231-241. doi: 10.1111/imm.13348. Epub 2021 May 22.
Inflammation and immune dysfunction have been increasingly recognized as crucial mechanisms in atherogenesis. Modifications in cell lipid metabolism, plasma dyslipidaemia and particularly low high-density lipoprotein (HDL) levels occur both in atherosclerosis and in autoimmune rheumatic diseases (which are strongly associated with an increased risk of atherosclerosis), suggesting the presence of a crucial link. HDL, the plasma lipoprotein responsible for reverse cholesterol transport, is known for its several protective effects in the context of atherosclerosis. Among these, HDL immunomodulatory effects are possibly the less understood. Through the efflux of cholesterol from plasma cell membranes with the consequent disruption of lipid rafts and the interaction with the cholesterol transporters present in the plasma membrane, HDL affects both the innate and adaptive immune responses. Animal and human studies have demonstrated a predominance of HDL anti-inflammatory effects, despite some pro-inflammatory actions having also been reported. The HDL role on the modulation of the immune response is further suggested by the detection of low levels together with a dysfunctional HDL in patients with autoimmune diseases. Here, we review the current knowledge of the immune mechanisms of atherosclerosis and the modulatory effects HDL may have on them.
炎症和免疫功能障碍已被越来越多地认为是动脉粥样硬化形成的关键机制。细胞脂质代谢、血浆血脂异常的改变，特别是低高密度脂蛋白（HDL）水平，既发生在动脉粥样硬化中，也发生在自身免疫性风湿病中（这些疾病与动脉粥样硬化风险的增加密切相关），这表明存在着一个关键的联系。HDL 是一种负责胆固醇逆向转运的血浆脂蛋白，其在动脉粥样硬化背景下具有多种保护作用。其中，HDL 的免疫调节作用可能是了解最少的。通过从细胞膜中排出胆固醇，从而破坏脂筏，并与质膜中存在的胆固醇转运蛋白相互作用，HDL 影响先天免疫和适应性免疫反应。动物和人类研究表明，尽管也有一些促炎作用的报道，但 HDL 主要具有抗炎作用。HDL 在调节免疫反应中的作用进一步提示，在自身免疫性疾病患者中检测到低水平和功能失调的 HDL。在这里，我们综述了动脉粥样硬化的免疫机制以及 HDL 可能对其产生的调节作用的最新知识。
