The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis.
The role of gut-derived oxidized lipids and bacterial lipopolysaccharide in systemic inflammation and atherosclerosis.
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DOI：
10.1097/mol.0000000000000841
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发表时间：
2022-10-01
影响因子：
4.4
通讯作者：
Fogelman, Alan M.
中科院分区：
文献类型：
--
作者：
Wang, Huan;Reddy, Srinivasa T.;Fogelman, Alan M.
关键词：
本文综述了肠道细菌脂多糖（LPS）和氧化磷脂导致慢性全身性炎症和动脉粥样硬化的机制。肠源性LPS通过两条不同的途径进入小肠，这两条途径涉及高密度脂蛋白（HDL）和乳糜微粒。肠来源的LPS可以结合到小肠中的LPS结合蛋白（LBP）和HDL 3，并通过门静脉行进到肝脏，在肝脏中它不引起炎症反应，并且被灭活，或者它可以结合到HDL 2并通过门静脉行进到肝脏，在肝脏中它引起炎症反应。或者，在小肠中，LPS可以结合LBP和乳糜微粒，并通过消化道进入体循环，增强炎症过程，包括动脉粥样硬化。在小肠中形成的氧化磷脂通过调节抗微生物蛋白如肠碱性磷酸酶来调节LPS在小肠中的水平和摄取。肠源性LPS和氧化磷脂可能是导致某些人感染人类免疫缺陷病毒后持续炎症的原因，这些人接受了强效抗逆转录病毒治疗，病毒水平无法检测到。通过靶向肠源性氧化磷脂，可以减少肠源性LPS的摄取，以减少全身炎症和动脉粥样硬化。
This review explores mechanisms by which gut-derived bacterial lipopolysaccharide (LPS) and oxidized phospholipids contribute to chronic systemic inflammation and atherosclerosis. Gut-derived LPS enters through the small intestine via two distinct pathways that involve high density lipoproteins (HDL) and chylomicrons. Gut-derived LPS can bind to the LPS-binding protein (LBP) and to HDL3 in the small intestine and travel through the portal vein to the liver where it does not elicit an inflammatory reaction, and is inactivated or it can bind to HDL2 and travel through the portal vein to the liver where it elicits an inflammatory reaction. Alternatively, in the small intestine, LPS can bind to LBP and chylomicrons and travel through the lymphatics to the systemic circulation and enhance inflammatory processes including atherosclerosis. Oxidized phospholipids formed in the small intestine regulate the levels and uptake of LPS in small intestine by regulating antimicrobial proteins such as intestinal alkaline phosphatase. Gut-derived LPS and oxidized phospholipids may be responsible for the persistent inflammation seen in some persons with human immunodeficiency virus on potent antiretroviral therapy with undetectable virus levels. By targeting gut-derived oxidized phospholipids, the uptake of gut-derived LPS may be reduced to decrease systemic inflammation and atherosclerosis.