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Dicarbonyl-Modified Low-Density Lipoproteins Are Key Inducers of LOX-1 and NOX1 Gene Expression in the Cultured Human Umbilical Vein Endotheliocytes

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Abstract

Expression of LOX-1 and NOX1 genes in the human umbilical vein endotheliocytes (HUVECs) cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that among the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), the MDA-modified LDLs caused the greatest induction of the LOX-1 and NOX1 genes, as well as of the genes of antioxidant enzymes and genes of proapoptotic factors in HUVECs. Key role of the dicarbonyl-modified LDLs in the molecular mechanisms of vascular wall damage and endothelial dysfunction is discussed.

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Abbreviations

CAT (CAT):

catalase

GL:

glyoxal

GPx (GPX):

glutathione peroxidases

HUVECs:

human umbilical vein endothelial cells

LDL:

low-density lipoproteins

LOOH:

lipid hydroperoxides

LOX-1 (LOX-1, OLR1),:

lectin-like oxidized LDL receptor-1

MDA:

malone dialdehyde

MGL:

methyl glyoxal

NOX1 (NOX1):

NADPH-oxidase 1

Prdx (PRDX):

peroxiredoxins

RCC:

reactive carbonyl compounds

ROS:

reactive oxygen species

SOD (SOD):

superoxide dismutase

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Funding

This work was financially supported by the Russian Science Foundation (grant no. 22-15-00013).

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Authors and Affiliations

  1. Chazov National Medical Research Center for Cardiology, 121552, Moscow, Russia

    Vadim Z. Lankin, Alla K. Tikhaze, Olga A. Antonova & Galina G. Konovalova

  2. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Mars G. Sharapov, Ruslan G. Goncharov & Vladimir I. Novoselov

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  1. Vadim Z. Lankin
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Contributions

V.Z.L. supervision of the study, writing the paper, discussion of the results; M.G.S. conducting molecular biological investigation, writing of the paper, discussion of the results, analysis of the literature; A.K.T. participation in writing and editing of the paper; R.G.G. conducting molecular biological investigation; O.A.A. preparation of the primary culture and cultivation of HUVECs; G.G.K. isolation of LDLs and preparation of dicarbonyl-modified LDLs; V.I.N. participation in writing and discussion of the paper.

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Correspondence to Mars G. Sharapov.

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Lankin, V.Z., Sharapov, M.G., Tikhaze, A.K. et al. Dicarbonyl-Modified Low-Density Lipoproteins Are Key Inducers of LOX-1 and NOX1 Gene Expression in the Cultured Human Umbilical Vein Endotheliocytes. Biochemistry Moscow 88, 2125–2136 (2023). https://doi.org/10.1134/S0006297923120143

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