SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients With low LDL-C levels
Open Access
- 1 January 2020
- journal article
- research article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 134 (2), 273-287
- https://doi.org/10.1042/CS20190459
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, [H-3]-cholesterol efflux rates were lower and mRNA levels of the inflammatory factors tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) 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-alpha and IFN-gamma by increasing liver X receptor (LXR)-beta levels. Furthermore, the degree of CpG island methylation in the SULT2B1 b 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-beta 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.This publication has 40 references indexed in Scilit:
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