Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis
Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. <i>ABCA1</i>, <i>ABCG1</i>, and SR-BI cholesterol transporters are involved in cholesterol...
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MDPI AG
2021-12-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/8/12/170 |
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| author | Alexandra V. Rozhkova Veronika G. Dmitrieva Elena V. Nosova Alexander D. Dergunov Svetlana A. Limborska Liudmila V. Dergunova |
| author_facet | Alexandra V. Rozhkova Veronika G. Dmitrieva Elena V. Nosova Alexander D. Dergunov Svetlana A. Limborska Liudmila V. Dergunova |
| author_sort | Alexandra V. Rozhkova |
| collection | DOAJ |
| description | Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. <i>ABCA1</i>, <i>ABCG1</i>, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i>, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of <i>ABCA1</i>, <i>ABCG1</i>, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review. |
| first_indexed | 2024-03-10T03:51:32Z |
| format | Article |
| id | doaj.art-3835903fd91749f5843e9243a198bb3d |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-10T03:51:32Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-3835903fd91749f5843e9243a198bb3d2023-11-23T08:54:53ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252021-12-0181217010.3390/jcdd8120170Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in AtherogenesisAlexandra V. Rozhkova0Veronika G. Dmitrieva1Elena V. Nosova2Alexander D. Dergunov3Svetlana A. Limborska4Liudmila V. Dergunova5Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, 123182 Moscow, RussiaDepartment of Molecular Bases of Human Genetics, Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, 123182 Moscow, RussiaDepartment of Molecular Bases of Human Genetics, Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, 123182 Moscow, RussiaLaboratory of Structural Fundamentals of Lipoprotein Metabolism, National Medical Research Center for Therapy and Preventive Medicine, 101990 Moscow, RussiaDepartment of Molecular Bases of Human Genetics, Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, 123182 Moscow, RussiaDepartment of Molecular Bases of Human Genetics, Institute of Molecular Genetics of National Research Center “Kurchatov Institute”, 123182 Moscow, RussiaAtheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. <i>ABCA1</i>, <i>ABCG1</i>, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i>, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of <i>ABCA1</i>, <i>ABCG1</i>, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review.https://www.mdpi.com/2308-3425/8/12/170<i>ABCA1</i><i>ABCG1</i>atherosclerosischolesterol effluxgene expression<i>SCARB1</i> |
| spellingShingle | Alexandra V. Rozhkova Veronika G. Dmitrieva Elena V. Nosova Alexander D. Dergunov Svetlana A. Limborska Liudmila V. Dergunova Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis Journal of Cardiovascular Development and Disease <i>ABCA1</i> <i>ABCG1</i> atherosclerosis cholesterol efflux gene expression <i>SCARB1</i> |
| title | Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis |
| title_full | Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis |
| title_fullStr | Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis |
| title_full_unstemmed | Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis |
| title_short | Genomic Variants and Multilevel Regulation of <i>ABCA1</i>, <i>ABCG1</i>, and <i>SCARB1</i> Expression in Atherogenesis |
| title_sort | genomic variants and multilevel regulation of i abca1 i i abcg1 i and i scarb1 i expression in atherogenesis |
| topic | <i>ABCA1</i> <i>ABCG1</i> atherosclerosis cholesterol efflux gene expression <i>SCARB1</i> |
| url | https://www.mdpi.com/2308-3425/8/12/170 |
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