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Your search keyword '"Ma, Pengjun"' showing total 2 results
Start Over Author "Ma, Pengjun" Topic atherosclerosis
2 results on '"Ma, Pengjun"'

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

Author

Guo W, Zhang H, Yang A, Ma P, Sun L, Deng M, Mao C, Xiong J, Sun J, Wang N, Ma S, Nie L, and Jiang Y

Subjects
Animals, Apolipoproteins E deficiency, Apolipoproteins E metabolism, Atherosclerosis complications, DNA Methylation genetics, Diet, Disease Progression, Down-Regulation genetics, Foam Cells metabolism, HEK293 Cells, Humans, Hyperhomocysteinemia complications, Hyperhomocysteinemia pathology, Male, Methionine, Mice, Inbred C57BL, Mice, Knockout, Models, Biological, Plaque, Atherosclerotic complications, Plaque, Atherosclerotic pathology, Promoter Regions, Genetic, Protein Binding, THP-1 Cells, DNA Methyltransferase 3B, Atherosclerosis metabolism, Atherosclerosis pathology, CD36 Antigens metabolism, DNA (Cytosine-5-)-Methyltransferases metabolism, Homocysteine adverse effects, Signal Transduction, Sp1 Transcription Factor metabolism
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., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2020
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2. Aberrant MFN2 transcription facilitates homocysteine-induced VSMCs proliferation via the increased binding of c-Myc to DNMT1 in atherosclerosis.

Author

Xu L, Hao H, Hao Y, Wei G, Li G, Ma P, Xu L, Ding N, Ma S, Chen AF, and Jiang Y

Subjects
Animals, Atherosclerosis pathology, Base Sequence, Cell Proliferation drug effects, GTP Phosphohydrolases metabolism, Gene Expression Regulation drug effects, Humans, Male, Mice, Inbred C57BL, Models, Biological, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle metabolism, Plaque, Atherosclerotic pathology, Promoter Regions, Genetic genetics, Protein Binding drug effects, Atherosclerosis genetics, DNA (Cytosine-5-)-Methyltransferase 1 metabolism, GTP Phosphohydrolases genetics, Homocysteine pharmacology, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle pathology, Proto-Oncogene Proteins c-myc metabolism, Transcription, Genetic drug effects
Abstract

It is well-established that homocysteine (Hcy) is an independent risk factor for atherosclerosis. Hcy can promote vascular smooth muscle cell (VSMC) proliferation, it plays a key role in neointimal formation and thus contribute to arteriosclerosis. However, the molecular mechanism on VSMCs proliferation underlying atherosclerosis is not well elucidated. Mitofusin-2 (MFN2) is an important transmembrane GTPase in the mitochondrial outer membrane and it can block cells in the G0/G1 stage of the cell cycle. To investigate the contribution of aberrant MFN2 transcription in Hcy-induced VSMCs proliferation and the underlying mechanisms. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase in atherosclerotic plaque of APOE -/- mice with hyperhomocystinaemia (HHcy) as well as in VSMCs exposed to Hcy in vitro. The DNA methylation level of MFN2 promoter was obviously increased in VSMCs treated with Hcy, leading to suppressed promoter activity and low expression of MFN2. In addition, we found that the expression of c-Myc was increased in atherosclerotic plaque and VSMCs treated with Hcy. Further study showed that c-Myc indirectly regulates MFN2 expression is duo to the binding of c-Myc to DNMT1 promoter up-regulates DNMT1 expression leading to DNA hypermethylation of MFN2 promoter, thereby inhibits MFN2 expression in VSMCs treated with Hcy. In conclusion, our study demonstrated that Hcy-induced hypermethylation of MFN2 promoter inhibits the transcription of MFN2, leading to VSMCs proliferation in plaque formation, and the increased binding of c-Myc to DNMT1 promoter is a new and relevant molecular mechanism., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Published
2019
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