SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients with low LDL-C levels.

Abstract

The current main treatment for coronary artery disease (CAD) is to reduce low-density lipoprotein cholesterol (LDL-C) by statins, which could decrease the incidence of major adverse cardiovascular events (MACEs) by 30%. However, many residual risks still remain. To clarify the mechanism involved, we studied patients with acute myocardial infarction (AMI) with low LDL-C levels. Lymphocytes were isolated, and it was found that despite no difference in plasma LDL-C level, the lymphocyte cholesterol content was higher in AMI patient than those in non-CAD patients; thus, the decrease in intracellular cholesterol content was inconsistent with that in the plasma. Additionally, [3H]-cholesterol efflux rates were lower and mRNA levels of the inflammatory factors tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) higher in AMI lymphocytes. It was found that sulphotransferase 2B1b (SULT2B1b) expression was higher in AMI lymphocytes. Further research using Jurkat T lymphocytes confirmed that SULT2B1b knockdown increased cholesterol efflux capacity and decreased mRNA levels of TNF-α and IFN-γ by increasing liver X receptor (LXR)-β levels. Furthermore, the degree of CpG island methylation in the SULT2B1b promoter was reduced in cells from AMI patients. In conclusion, SULT2B1b up-regulation due to hypomethylation of its promoter promotes cholesterol accumulation and inflammation by inhibiting LXR-β in lymphocytes of AMI patients with low LDL-C levels. Therefore, reducing intracellular cholesterol is also important as plasma cholesterol levels. Therapeutic approaches to decrease SULT2B1b expression might be potentially beneficial for CAD prevention by decreasing intracellular cholesterol.

• Authors: Yanan Zhang, Zhongzhou Guo, Tongwei Wu, Jichen Liu, Bin Zhang, Wenyan Lai, Wenwei Tu, Zhigang Guo, Tiantian Luo
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 134 Issue 2 Pg. 273-287 (Jan 31 2020) ISSN: 1470-8736 [Electronic] England
• PMID: 31957803 (Publication Type: Journal Article)
• Copyright: © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Chemical References

• Cholesterol, LDL
• Inflammation Mediators
• Liver X Receptors
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• Cholesterol
• Sulfotransferases
• SULT2B1 protein, human

Topics

• Biological Transport
• Cholesterol (blood, metabolism)
• Cholesterol, LDL (metabolism)
• Coronary Artery Disease (genetics, metabolism, prevention & control)
• DNA Methylation
• Humans
• Inflammation Mediators (metabolism)
• Interferon-gamma (genetics, metabolism)
• Jurkat Cells
• Liver X Receptors (genetics, metabolism)
• Lymphocytes (metabolism)
• Myocardial Infarction (genetics, metabolism, prevention & control)
• Promoter Regions, Genetic (genetics)
• Sulfotransferases (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)