Research advances on the role of ACSL3 in the atherosclerosis / 生理学报

Lipids droplets are organelles that store neutral lipids and are closely related to lipid accumulation. Long chain acyl-coenzyme A synthetase 3 (ACSL3) is a lipid droplet-associated protein mainly distributed in the cell membrane, endoplasmic reticulum, and intracellular lipid droplets, and its distribution depends on cell type and fatty acid supply. ACSL3 is a key regulator of fatty acid metabolism that is closely related to intracellular lipid accumulation, and plays an important role in various pathophysiological processes such as lipid droplet synthesis and lipid metabolism, cellular inflammation, and ferroptosis. This paper mainly reviews the role of ACSL3 in lipid synthesis, ferroptosis, and inflammatory response, with focus on the mechanism of its role in lipid accumulation in atherosclerosis, and provides new ideas for exploring potential therapeutic targets in atherosclerotic diseases.

Research Progress of ACSL3 and Related Diseases / 中国生物化学与分子生物学报

Lipid droplets are important organelles that have the function of storing intracellular lipid and regulation of cell lipid homeostasis. A variety of lipid droplet-related proteins exists on the surface of lipid droplets. The acyl CoA long chain synthetase 3 (ACSL3) of the long chain acyl-CoA synthetase family is a kind of lipid droplet-related protein and an essential enzyme in the process of biosynthesis. ACSL3, which plays different roles in a variety of pathophysiological processes such as the synthesis of lipid droplets, the regulation of autophagy, and cell iron death, is widely distributed on the surface of lipid droplets in most cells. In addition, many studies have shown that ACSL3 is also widely involved in the occurrence and development of atherosclerosis, nonalcoholic fatty liver disease, diabetes, and tumors. At present, domestic research on ACSL3 is relatively focused on the relationship between ACSL3 and animal breeding and growth. However, the reports on the mechanism of ACSL3 in lipid metabolism and the relationship between ACSL3 and diseases are relatively rare. This article summarizes the structure of ACSL3 and its mechanism in cell lipid metabolism and related diseases, which may provide a new theoretical basis for the prevention and treatment of atherosclerosis, non-alcoholic fatty liver disease, diabetes and other ACSL3 related diseases. This article also further explores the role of ACSL3 in the process of lipid droplet synthesis, autophagy, and iron death.

NADPH oxidase activity does not affect cellular cholesterol loading in vascular smooth muscle cells / 生理学报

Reactive oxygen species generated by NADPH oxidase enhance aortic vascular smooth muscle cell proliferation and migration which play an important role in the pathophysiology of atherosclerosis. We investigated the role of NADPH oxidase in the cellular cholesterol metabolism in vascular smooth muscle cells using p47phox-deficient cells. Wild-type and p47phox knockout vascular smooth muscle cells were loaded with cholesterol for 72 h by using 10 mg/L cholesterol:methyl-beta-cyclodextrin complexes and then incubated with or without 0.3 mg/L thrombin for 10 min. Foam cell formation was determined by accumulation of intracellular cholesterol, oil Red O-stained lipid droplets. After cholesterol loading, cellular lipid droplets raised sharply, cellular cholesterol increased from (31.4+/-2.0) to (61.0+/-2.1) mg/g protein (P<0.05) in wild-type cells, and from (29.8+/-2.5) to (51.3+/-3.1) mg/g protein (P<0.05) in p47phox deficient cells, but the difference between the two cell types was not significant. Immunostaining showed decreased levels of smooth muscle alpha-actin and increased levels of macrophage marker Mac-2 in both wild-type and p47phox deficient vascular smooth muscle cells. One of the macrophage-related inflammation genes, monocyte chemoattractant protein-1 (MCP-1) expression did not change in both two cell types detected by immunostaining. Although additional incubating with thrombin, another macrophage-related inflammation gene, vascular cell adhesion molecule-1 (VCAM-1) expression was similar in all groups analyzed by real-time RT-PCR. However, the expression of ATP-binding cassette transporter A1 (ABCA1), acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1), the key proteins in cellular cholesterol metabolism, were similarly increased (P<0.05) in both two cell types as determined by quantitative real-time RT-PCR and Western blot, and it was not related to the state of oxidative stress. Interestingly, the expression of adipophilin, the lipid droplet related protein, had the similar results with ABCA1 and ACAT1, but, in wild-type cells, its expression also increased merely incubating with thrombin as determined by quantitative real-time RT-PCR. Together, these results suggest that p47phox-dependent NADPH oxidase is not involved in transdifferentitation of vascular smooth muscle cells into macrophage-like state after cholesterol loading. Deleting p47phox gene does not affect the cellular cholesterol metabolism in vascular smooth muscle cells.