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.
Uvod: Cilj rada je otkrivanje povezanosti nivoa lipoproteinskog holesterola visoke gustine u plazmi (HDL-C) sa nivoom transkripta anotiranih gena u mononuklearnim ćelijama periferne krvi (PBMC), a koji su uključeni u HDL metabolizam i aterogenezu u odsustvu morfološki evidentne koronarne stenoze.
Metode: Izmereni su nivoi transkripta 63 gena u PBMC kod 38 pacijenata muškog pola starosti između 40 i 60 godina bez koronarne ateroskleroze sa značajno raznovrsnim nivoom HDL-C. Interakcije proteina su analizirane pomoću STRING baze podataka.
Rezultati: Među 22 gena povezana sa HDL, nivoi transkripta za 10 gena (ABCA1, BMP1, CUBN, HDLBP, LCAT, LDLR, PRKACB, PRKACG, SCARB1 i ZDHHC8) su bili u negativnoj korelaciji sa HDL-C, dok je korelacija pozitivna za GEN APOA1. Od 41 gena koji su skloni aterosklerozi, nivoi transkripta za 11 gena (CSF1R, CSF2RB, IL18R1, ITGAM, ITGB3, PRKCK, SREBF1, TLR5, TLR8, TNFRSF1A i TNFRSF1B) su u negativnoj korelaciji samo sa HDL-C, ali ne sa LL-C-C, i TG u plazmi. Proteinski proizvodi efikasno su delovali u svakom klasteru, dok su između klastera postojala samo dva čvora preseka.
Zaključak: Predlaže se koordinisana regulacija priliva i odliva holesterola u PBMC kod subjekata bez ateroskleroze sa širokim opsegom vrednosti nivoa HDL-C. Smanjena sinteza i transport holesterol estra do jetre može doprineti hiperalfalipoproteinemiji. Povećanje HDL-C povezano je sa smanjenjem ekspresije gena u vezi sa urođenim imunitetom i upalnim procesima. Vizualizacija ovih 22 gena može biti korisna u validaciji HDL funkcionalnosti i aterogeneze, čak i u odsustvu morfološki vidljive koronarne stenoze.
Keywords: HDL and atherogenesis-prone genes; HDL functionality; atherogenesis; gene expression; human PBMC.
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.