Nature review immunology: cholesterol inflammatory response and atherosclerosis January 27, 2015 Source: Bio Valley bioon.com Since entering the industrialized society, people's diet has undergone great changes. Long-term consumption of foods rich in fats and sterols increases the cholesterol-rich low-density lipoprotein (LDL) content in the blood system, promotes excessive deposition of cholesterol on the arterial wall, and causes inflammation and ultimately atherosclerosis. hardening. After modification, LDL acts as a ligand for a class of cell surface TLRs, which can trigger an innate immune response. Macrophages are modified to induce phagocytosis after LDL stimulation, resulting in the accumulation of cholesterol in the cells. It will also enhance the next round of immune response. On the other hand, high-density lipoprotein (HDL) transports cholesterol from the cytoplasm and outwards, a process that controls the immune response. The above indicates that the accumulation of cholesterol in the cytosol can regulate the immune response. But how did this happen? Reverse sterol transport ( RCT ) and inflammatory response: The extracellular transport of cholesterol is dependent on the transporters ABCA1 and ABCG1. Recent studies have found that LPS stimulation can reduce the activity of ABCG1 and ABCA1, thereby reducing the ability of macrophages to clear cholesterol. . In turn, HDL secreted by the liver and small intestine can bind to LPS, thereby inhibiting its ability to produce an immune response. In addition, during acute infection, the normal function of HDL is lost and it is converted from anti-inflammatory molecules to pro-inflammatory molecules. The study found that in the inflammatory stimulation of atherosclerotic wounds, macrophage myeloperoxidase (MPO) activity increased, HDL was oxidized, causing loss of function; in addition, cholesterol transport receptor ABCA1 will also be MPO Oxidation causes a decrease in the ability of cholesterol to transport outward. Inflammatory response mechanism caused by cholesterol accumulation: Many studies have confirmed that modified LDL can act as a type of ligand to cause macrophage immune response, and the mechanism of action is the same as LPS. In addition, the extracellular transport of cholesterol can inhibit the immune response. Conversely, the intracellular accumulation of cholesterol can play a role in promoting the inflammatory response. So how is this effect achieved? The study found that the content of cholesterol in the macrophages of ABCA1 and ABCG1 was increased, and the immune response was stronger after TLR stimulation, and stronger apoptosis occurred when LDL was stimulated. Macrophage-specific ABCA1 and ABCG1-deficient mice produced more pronounced atherosclerotic symptoms, and a large accumulation of cholesterol in the lesion caused the formation of cholesterol crystals. Studies have shown that macrophage phagocytosis of cholesterol crystals or cholesterol crystals formed inside macrophages can cause activation of inflammatory bodies. Activation of inflammatory bodies is dependent on a two-step signal: NFkB priming and inflammasome aggregation. The former has been shown to be produced by modified LDL-stimulated TLRs, which are currently presumed to be caused by post-cholesterol crystals. In recent years, there have been many articles revealing the role of cholesterol crystals in the activation of inflammatory bodies, but there is no clear conclusion yet. Negative regulation of inflammatory response: First, the LXR transcription factor is a key protein that inhibits the inflammatory response caused by cholesterol. It promotes the extracellular transport of cholesterol through ABCA1 and ABCG1. At the same time, LXR can promote the expression of some genes that regulate the synthesis of unsaturated fatty acids, which can inhibit the activity of NF-kB, and so on. It is worth noting that the accumulation of cholesterol in macrophages feedbacks to inhibit the formation of endogenous cholesterol. It allows intracellular accumulation of a large amount of cholesterol precursor, streptohol, which regulates the expression of LXR. The above description shows that cholesterol also has an effect of promoting an inflammatory reaction and suppressing an inflammatory reaction. Finally, during atherosclerosis, cholesterol also directs the differentiation and migration of a large number of bone marrow cells. Currently, drugs for the treatment of atherosclerosis are mainly statins responsible for lowering the cholesterol content in LDL. However, such drugs have very strong side effects. Based on the above facts, LXR and drugs that increase HDL levels in humans or activate APOA1 (a class of HDL transporters) are considered to be an important target for anti-atherosclerosis as the first choice for drug development. Original link: http://news.bioon.com/article/6665222.html China Extract Powder For Use As Dietary Supplement Extract Powder, Extract Powder Manufacturer Shaanxi Kang New Pharmaceutical co., Ltd. , https://www.anabolicsteriod.com