Homocysteine accelerates atherosclerosis by inhibiting scavenger receptor class B member1 via DNMT3b/SP1 pathway.

Abstract

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, which is characterized by lipid accumulation in the atherosclerotic plaque. Increasing evidence supports that as the main receptor of high-density lipoprotein, scavenger receptor class B member 1 (SCARB1) is protective against atherosclerosis. However, the underlying mechanism regarding it in Hcy-mediated atherosclerosis remains unclear. Here, we found the remarkable inhibition of SCARB1 expression in atherosclerotic plaque and Hcy-treated foam cells, whereas overexpression of SCARB1 can suppress lipid accumulation in foam cells following Hcy treatment. Analysis of SCARB1 promoter showed that no significant change of methylation level was observed both in vivo and in vitro under Hcy treatment. Moreover, it was found that the negative regulation of DNMT3b on SCARB1 was due to the decreased recruitment of SP1 to SCARB1 promoter. Thus, we concluded that inhibition of SCARB1 expression induced by DNMT3b at least partly accelerated Hcy-mediated atherosclerosis through promoting lipid accumulation in foam cells, which was attributed to the decreased binding of SP1 to SCARB1 promoter. In our point, these findings will provide novel insight into an epigenetic mechanism for atherosclerosis.

• Authors: Wei Guo, Huiping Zhang, Anning Yang, Pengjun Ma, Lei Sun, Mei Deng, Caiyan Mao, Jiantuan Xiong, Jianmin Sun, Nan Wang, Shengchao Ma, Lihong Nie, Yideng Jiang
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 138 Pg. 34-48 (01 2020) ISSN: 1095-8584 [Electronic] England
• PMID: 31733201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Apolipoproteins E
• CD36 Antigens
• Sp1 Transcription Factor
• Homocysteine
• Methionine
• DNA (Cytosine-5-)-Methyltransferases
• DNA methyltransferase 3B

Topics

• Animals
• Apolipoproteins E (deficiency, metabolism)
• Atherosclerosis (complications, metabolism, pathology)
• CD36 Antigens (metabolism)
• DNA (Cytosine-5-)-Methyltransferases (metabolism)
• DNA Methylation (genetics)
• Diet
• Disease Progression
• Down-Regulation (genetics)
• Foam Cells (metabolism)
• HEK293 Cells
• Homocysteine (adverse effects)
• Humans
• Hyperhomocysteinemia (complications, pathology)
• Male
• Methionine
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Biological
• Plaque, Atherosclerotic (complications, pathology)
• Promoter Regions, Genetic
• Protein Binding
• Signal Transduction
• Sp1 Transcription Factor (metabolism)
• THP-1 Cells