HDL cholesterol is associated with pbmc expression of genes involved in HDL metabolism and atherogenesis
To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis. Tran...
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Published in | Journal of medical biochemistry Vol. 39; no. 3; pp. 372 - 383 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Serbia
Society of Medical Biochemists of Serbia, Belgrade
02.09.2020
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Online Access | Get full text |
ISSN | 1452-8266 1452-8258 1452-8266 |
DOI | 10.2478/jomb-2019-0052 |
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Abstract | To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis.
Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database.
Among 22 HDL-related genes, the transcript levels for 10 genes (
and
) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes (
and
) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters.
Coordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis. |
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AbstractList | Background: To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis. Methods: Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database. Results: Among 22 HDL-related genes, the transcript levels for 10 genes (ABCA1, BMP1, CUBN, HDLBP, LCAT, LDLR, PRKACB, PRKACG, SCARB1 and ZDHHC8) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes (CSF1R, CSF2RB, IL18R1, ITGAM, ITGB3, PRKCQ, SREBF1, TLR5, TLR8, TNFRSF1A and TNFRSF1B) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters. Conclusions: Coordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis. To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis.BACKGROUNDTo reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis.Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database.METHODSTranscript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database.Among 22 HDL-related genes, the transcript levels for 10 genes (ABCA1, BMP1, CUBN, HDLBP, LCAT, LDLR, PRKACB, PRKACG, SCARB1 and ZDHHC8) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes (CSF1R, CSF2RB, IL18R1, ITGAM, ITGB3, PRKCQ, SREBF1, TLR5, TLR8, TNFRSF1A and TNFRSF1B) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters.RESULTSAmong 22 HDL-related genes, the transcript levels for 10 genes (ABCA1, BMP1, CUBN, HDLBP, LCAT, LDLR, PRKACB, PRKACG, SCARB1 and ZDHHC8) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes (CSF1R, CSF2RB, IL18R1, ITGAM, ITGB3, PRKCQ, SREBF1, TLR5, TLR8, TNFRSF1A and TNFRSF1B) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters.Coordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis.CONCLUSIONSCoordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis. To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral blood mononuclear cells (PBMC) and involved in HDL metabolism and atherogenesis at the absence of morphologically evident coronary stenosis. Transcript levels of 63 genes in PBMC from 38 male patients 40-60 years without coronary atherosclerosis with widely varied HDL-C level were measured. The protein interactions were analyzed with STRING database. Among 22 HDL-related genes, the transcript levels for 10 genes ( and ) negatively correlated with HDL-C, while positively for APOA1 gene. Among 41 atherosclerosis-prone genes, the transcript levels for 11 genes ( and ) negatively correlated with HDL-C only, not with LDL-C and plasma TG. The protein products efficiently interacted within each cluster while only two intersection nodes existed between clusters. Coordinate regulation of cholesterol influx and efflux in PBMC in atherosclerosis-free subjects with widely varied HDL-C level is suggested. The decreased synthesis and transport of cholesteryl ester to the liver may contribute to hyperalphalipoproteinemia. HDL-C increase is associated with the decrease of expression of innate immunity and inflammation genes. Visualization of 22 responder genes is suggested to be useful in the validation of HDL functionality and atherogenesis even at the absence of morphologically evident coronary stenosis. |
Author | Nosova, Elena V. Bazaeva, Ekaterina V. Dergunova, Liudmila V. Dmitrieva, Veronika G. Rozhkova, Alexandra V. Dergunov, Alexander D. Limborska, Svetlana A. |
AuthorAffiliation | 2 National Research Centre for Preventive Medicine, Laboratory of Structural Fundamentals of Lipoprotein Metabolism, Moscow, Russia 1 Institute of Molecular Genetics of the Russian Academy of Sciences, Laboratory of Functional Genomics, Moscow, Russia |
AuthorAffiliation_xml | – name: 1 Institute of Molecular Genetics of the Russian Academy of Sciences, Laboratory of Functional Genomics, Moscow, Russia – name: 2 National Research Centre for Preventive Medicine, Laboratory of Structural Fundamentals of Lipoprotein Metabolism, Moscow, Russia |
Author_xml | – sequence: 1 givenname: Liudmila V. surname: Dergunova fullname: Dergunova, Liudmila V. organization: Laboratory of Functional Genomics, Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, Russia – sequence: 2 givenname: Elena V. surname: Nosova fullname: Nosova, Elena V. organization: Laboratory of Functional Genomics, Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, Russia – sequence: 3 givenname: Veronika G. surname: Dmitrieva fullname: Dmitrieva, Veronika G. organization: Laboratory of Functional Genomics, Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, Russia, Laboratory of Structural Fundamentals of Lipoprotein Metabolism, National Research Centre for Preventive Medicine, Moscow, Russia – sequence: 4 givenname: Alexandra V. surname: Rozhkova fullname: Rozhkova, Alexandra V. organization: Laboratory of Functional Genomics, Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, Russia – sequence: 5 givenname: Ekaterina V. surname: Bazaeva fullname: Bazaeva, Ekaterina V. organization: Laboratory of Structural Fundamentals of Lipoprotein Metabolism, National Research Centre for Preventive Medicine, Moscow, Russia – sequence: 6 givenname: Svetlana A. surname: Limborska fullname: Limborska, Svetlana A. organization: Laboratory of Functional Genomics, Institute of Molecular Genetics of the Russian Academy of Sciences, Moscow, Russia – sequence: 7 givenname: Alexander D. surname: Dergunov fullname: Dergunov, Alexander D. organization: Laboratory of Structural Fundamentals of Lipoprotein Metabolism, National Research Centre for Preventive Medicine, Moscow, Russia |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33269026$$D View this record in MEDLINE/PubMed |
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Cites_doi | 10.1056/NEJMoa1409065 10.1194/jlr.M200235-JLR200 10.1038/nature09270 10.1021/bi0485629 10.1038/nrcardio.2015.124 10.2174/138161210791051013 10.1093/nar/30.9.e36 10.1007/s00018-004-4090-3 10.1194/jlr.M600403-JLR200 10.1056/NEJMoa064278 10.1186/s12864-017-3533-9 10.1021/bi700028u 10.1002/lipd.12104 10.1021/bi00188a030 10.1038/9504 10.2478/jomb-2018-0041 10.1097/01.mol.0000226117.43178.7c 10.1074/jbc.M313487200 10.1074/jbc.M312476200 10.1194/jlr.R001610 10.1161/CIRCRESAHA.108.193011 10.1161/ATVBAHA.108.168690 10.1042/BJ20151000 10.1007/s11883-018-0715-0 10.1093/nar/gky1131 10.1002/jcp.27028 10.1681/ASN.2013060671 10.1161/01.ATV.17.11.2350 10.1001/jama.299.21.2524 10.1161/01.ATV.15.11.1987 10.1016/j.jacc.2017.04.052 10.3103/S0891416818020064 10.1161/01.ATV.19.1.159 10.1074/jbc.275.16.12003 10.1007/s00109-005-0030-4 |
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Copyright | 2020 Liudmila V. Dergunova, Elena V. Nosova, Veronika G. Dmitrieva, Alexandra V. Rozhkova, Ekaterina V. Bazaeva, Svetlana A. Limborska, Alexander D. Dergunov, published by CEON/CEES. 2020 Liudmila V. Dergunova, Elena V. Nosova, Veronika G. Dmitrieva, Alexandra V. Rozhkova, Ekaterina V. Bazaeva, Svetlana A. Limborska, Alexander D. Dergunov, published by CEON/CEES 2020 Society of Medical Biochemists of Serbia, Belgrade |
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Keywords | atherogenesis HDL functionality HDL and atherogenesis-prone genes human PBMC gene expression |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Correspondence to: Liudmila V. Dergunova, PhD, 2, Kurchatov square, 123182 Moscow, Russia lvdergunova@mail.ru |
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Snippet | To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in peripheral... Background: To reveal the association of plasma level of high density lipoprotein cholesterol (HDL-C) level with the transcript level of annotated genes in... |
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SubjectTerms | atherogenesis gene expression hdl and atherogenesis-prone genes hdl functionality human pbmc Original Paper |
Title | HDL cholesterol is associated with pbmc expression of genes involved in HDL metabolism and atherogenesis |
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