HDL as Bidirectional Lipid Vectors: Time for New Paradigms.
HDL as Bidirectional Lipid Vectors: Time for New Paradigms.
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DOI：
10.3390/biomedicines10051180
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发表时间：
2022-05-20
期刊：
影响因子：
4.7
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中科院分区：
文献类型：
--
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高密度脂蛋白（HDL）的抗动脉粥样硬化特性主要通过胆固醇从外周组织向肝脏的逆向转运（RCT）来解释。RCT似乎同意HDL胆固醇水平和冠状动脉疾病之间的负流行病学相关性。然而，旨在增加HDL胆固醇的治疗未能降低心血管风险，尽管它们有能力改善胆固醇流出，RCT的第一阶段。因此，HDL的心脏保护作用可能无法通过RCT来解释，现在是时候对这些脂蛋白的生理功能进行新的研究了。应该考虑的是，主要的HDL载脂蛋白，载脂蛋白AI，在整个进化过程中一直高度保守。因此，这些脂蛋白发挥着重要的生理作用，超出了它们的能力，以防止动脉粥样硬化。我们建议HDL作为双向脂质载体，根据其局部情况携带脂质从组织和组织。由HDL介导的脂质内流似乎对损伤发生部位的组织修复特别重要，包括动脉粥样硬化第一阶段的动脉。相比之下，HDL-脂质流出与分泌细胞相关，其中胞内囊泡的融合使细胞质膜急剧扩大，具有细胞功能受损的潜在后果。在这种情况下，HDL可以提供一些功能性脂质，不仅可以摄取胆固醇，还可以摄取过量的膜的组成部分，恢复分泌细胞的活力。这一假说与HDL对动脉粥样硬化的有益作用以及它们诱导胰岛素分泌的能力是一致的，值得进行实验探索。
The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.
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