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Review
. 2021 May 25;9(6):600.
doi: 10.3390/biomedicines9060600.

Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside

Alexandre Mezentsev  1 , Evgeny Bezsonov  2   3 , Dmitry Kashirskikh  2 , Mirza S Baig  4 , Ali H Eid  5   6 , Alexander Orekhov  2
Affiliations
Review

Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside

Alexandre Mezentsev et al. Biomedicines. .

Abstract

This review summarizes the main achievements in basic and clinical research of atherosclerosis. Focusing on desialylation as the first and the most important reaction of proatherogenic pathological cascade, we speak of how desialylation increases the atherogenic properties of low density lipoproteins and decreases the anti-atherogenic properties of high density lipoproteins. The separate sections of this paper are devoted to immunogenicity of lipoproteins, the enzymes contributing to their desialylation and animal models of atherosclerosis. In addition, we evaluate the available experimental and diagnostic protocols that can be used to develop new therapeutic approaches for atherosclerosis.

Keywords: HDL; LDL; animal models of atherosclerosis; anti-LDL antibodies; apolipoproteins; atherogenesis; desialylation; diagnostics of atherosclerosis; sialidase; trans-sialidase; treatment options for atherosclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The mechanism of enzyme reaction catalyzed by sialidase. Sialidase hydrolyzes the terminal Sia residue of glycolipids and glycoproteins. Sialosyl cation (in the square brackets), the transition state complex of the reaction; Neu5Ac2en-2-deoxy-2, 3-didehydro-D-N-acetylneuraminic acid, the unsaturated derivative of sialic acid.
Figure 2
Figure 2
The life cycle of influenza virus. Approaching the cell surface the virus (a) cleaves Sia residues (b) by viral sialidase from the decoy receptors (1) allowing the viral hemagglutinin to interact with the entry receptors and enter the host cell by endocytosis (2). After releasing from the endosome viral RNAs translocate to the nucleus (3) to replicate the genome and synthesize mRNAs (d). Then, viral mRNAs translate to viral proteins in the cytoplasm and viral mRNAs and proteins (e) assemble virions (4) that quit the cell by budding. The released virions infect the other host cells (5). (c) - transmembrane domain of the decoy receptor.
Figure 3
Figure 3
Desialylation of plasma proteins by immobilized sialidase in vivo. Green bars—control animals treated with saline (N = 10); Red bars—animals treated with immobilized sialidase (N = 10). The data are represented as mean ± SE.
See this image and copyright information in PMC

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