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- Publisher Website: 10.1042/CS20190459
- Scopus: eid_2-s2.0-85078687489
- PMID: 31957803
- WOS: WOS:000512417900012
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Article: SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients with low LDL-C levels
Title | SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients with low LDL-C levels |
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Authors | |
Keywords | acute myocardial infarction Atherosclerosis DNA methylation inflammation reverse cholesterol transport |
Issue Date | 2020 |
Publisher | Portland Press Ltd. The Journal's web site is located at http://www.clinsci.org/ |
Citation | Clinical Science, 2020, v. 134 n. 2, p. 273-287 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/289824 |
ISSN | 2023 Impact Factor: 6.7 2023 SCImago Journal Rankings: 1.565 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhang, Y | - |
dc.contributor.author | Guo, Z | - |
dc.contributor.author | Wu, T | - |
dc.contributor.author | Liu, J | - |
dc.contributor.author | Zhang, B | - |
dc.contributor.author | Lai, W | - |
dc.contributor.author | Tu, W | - |
dc.contributor.author | Guo, Z | - |
dc.contributor.author | Luo, T | - |
dc.date.accessioned | 2020-10-22T08:17:59Z | - |
dc.date.available | 2020-10-22T08:17:59Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Clinical Science, 2020, v. 134 n. 2, p. 273-287 | - |
dc.identifier.issn | 0143-5221 | - |
dc.identifier.uri | http://hdl.handle.net/10722/289824 | - |
dc.description.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. | - |
dc.language | eng | - |
dc.publisher | Portland Press Ltd. The Journal's web site is located at http://www.clinsci.org/ | - |
dc.relation.ispartof | Clinical Science | - |
dc.rights | The final version of record is available at [Journal URL]. | - |
dc.subject | acute myocardial infarction | - |
dc.subject | Atherosclerosis | - |
dc.subject | DNA methylation | - |
dc.subject | inflammation | - |
dc.subject | reverse cholesterol transport | - |
dc.title | SULT2B1b inhibits reverse cholesterol transport and promotes cholesterol accumulation and inflammation in lymphocytes from AMI patients with low LDL-C levels | - |
dc.type | Article | - |
dc.identifier.email | Tu, W: wwtu@hku.hk | - |
dc.identifier.authority | Tu, W=rp00416 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1042/CS20190459 | - |
dc.identifier.pmid | 31957803 | - |
dc.identifier.scopus | eid_2-s2.0-85078687489 | - |
dc.identifier.hkuros | 316634 | - |
dc.identifier.volume | 134 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 273 | - |
dc.identifier.epage | 287 | - |
dc.identifier.isi | WOS:000512417900012 | - |
dc.publisher.place | United Kingdom | - |
dc.identifier.issnl | 0143-5221 | - |