Atherosclerotic plaque contains materials, such as cholesterol, oxysterols, cell debris, modified fatty acids, and infiltrated cells. Among them, cholesterol is the major component in plaque. Cholesterol is known to originate from the influx of extracellular materials, but this explanation is not enough for the cholesterol accumulation observed in atherosclerotic plaque. This study examined the origins of cholesterols in plaques. The main focus was to determine if the intracellular cholesterol levels are affected by oxysterols in human vascular smooth muscle cells. The results showed that the cholesterol levels increased in response to a 7-ketocholesterol (7K)-treatment in a dose-dependent manner. Eight enzymes involved in cholesterol biosynthesis were examined. Among them, squalene epoxidase (SQLE) was increased by 7K but not by 7α-hydroxycholesterol, 27-hydroxycholesterol (27OH-chol), or cholesterol. The 7K-induced SQLE expression was suppressed in the presence of the enzyme inhibitor SB203580 but not by UO126 and SP600125. The SQLE immunoreactivity was detected in the atherosclerotic plaque of the aortic roots from apoE mice. In addition, 7K increased the cholesterol level and SQLE expression in murine bone marrow-derived macrophages. This suggests that 7K increases the intracellular cholesterol level through an elevation of SQLE expression, which might affect the progress of cholesterol accumulation in the atherosclerotic lipid core.
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http://dx.doi.org/10.1097/FJC.0b013e31825c3ddc | DOI Listing |
Comb Chem High Throughput Screen
January 2025
Department of Endocrinology and Metabolism, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, China.
Aims And Objectives: This study aimed to explore the relationship between HERC6- associated immune response and Non-Alcoholic Fatty Liver Disease (NAFLD) and to screen drug candidates for novel treatments.
Materials And Methods: Mendelian Randomization (MR) was performed to test the relationship between a genetically predicted increase in HERC6 expression and the development of NAFLD. A single-cell RNA-seq profile of liver tissue with histological characteristics (GSE168933) was obtained.
Mol Biol Rep
January 2025
Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, Queen Square House, London, WC1N 3BG, UK.
Background: Male EBP disorder with neurologic defects (MEND syndrome) is an extremely rare disorder with a prevalence of less than 1/1,000,000 individuals worldwide. It is inherited as an X-linked recessive disorder caused by impaired sterol biosynthesis due to nonmosaic hypomorphic EBP variants. MEND syndrome is characterized by variable clinical manifestations including intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities.
View Article and Find Full Text PDFPhytother Res
January 2025
School of Pharmacy, Minzu University of China, Beijing, China.
Saponins are compounds composed of lipophilic aglycones linked to hydrophilic sugars. Natural saponins are isolated from plants and some Marine organisms. As important cholesterol-lowering drugs, natural saponins have attracted wide attention for their therapeutic potential in a variety of cholesterol-related metabolic diseases.
View Article and Find Full Text PDFAs an advanced nucleic acid therapeutical modality, mRNA can express any type of protein in principle and thus holds great potential to prevent and treat various diseases. Despite the success in COVID-19 mRNA vaccines, direct local delivery of mRNA into the lung by inhalation would greatly reinforce the treatment of pulmonary pathogens and diseases. Herein, we developed lipid nanoparticles (LNPs) from degradable ionizable glycerolipids for potent pulmonary mRNA delivery via nebulization.
View Article and Find Full Text PDFDiabetol Metab Syndr
January 2025
Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Background: The potential therapeutic role of magnesium (Mg) in type 2 diabetes mellitus (T2DM) remains insufficiently studied despite its known involvement in critical processes like lipid metabolism and insulin sensitivity. This study examines the impact of Mg-focused nutritional education on lipid profile parameters, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in T2DM patients.
Methods: Thirty participants with T2DM were recruited for this within-subject experimental study.
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