SULT2B1b Inhibits Reverse Cholesterol Transport And Promotes Inflammation In Lymphocytes From AMI Patients With Low LDL-C Levels

BackgroundThe 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.ObjectiveTo clarify the mechanism involved,we studied patients with acute myocardial infarction(AMI)with low LDL-C levels.Methods and ResultsLymphocytes 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 TNF-? and IFN-y higher in AMI lymphocytes.It was found that sulfotransferase 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-? and IFN-? by increasing LXR-? levels.Furthermore,the degree of CpG island methylation in the SULT2B1b promoter was reduced in cells from AMI patients.ConclusionIn conclusion,SULT2Blb upregulation due to hypomethylation of its promoter promotes cholesterol accumulation and inflammation by inhibiting LXR-? in lymphocytes of AMI patients with low LDL-C levels.SignificanceTherefore,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.