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Alipov et al. Difference between native and desialylated LDL

considered as a possible mechanism of macrophage modified LDL and lipoprotein-containing immune
down-regulation. [14] complexes (LDL-CIC) in the plasma. Immunoglobulin G
(IgG) antibodies with high affinity for in vitro desialylated
While some studies found no differences in lipid peroxide and malondialdehyde-modified LDL were detected
content between native and desialylated LDL, [73] Others in patients with angiographically assessed coronary
reported that desialylation may cause both an increase atherosclerosis. On the other hand these antibodies
and decrease in susceptibility to oxidation depending have low affinity for native, glycated, acetylated, and
on LDL density and hyperlipidemia type. [74,75] Small LDL with other chemical modifications. [83] It was shown
dense LDL in type IIa hyperlipidemia was the most that IgG (subclasses G1, G3) against modified LDL
susceptible to oxidation. [75] Increased lipid peroxidation have pro-atherogenic properties, while IgM antibodies
was found in desialylated LDL. [76] Another study showed are atheroprotective. [14,84] In 2013 Montano [85] and
that LDL sialic acid levels negatively correlates with colleagues showed that monoclonal anti-oxLDL
thiobarbituric acid reactive substances and suggested IgM (E06) inhibited oxLDL binding to macrophages
that reactive oxygen substances may affect enzymatic in a dose dependent manner. Studies on LDL-
desialylation in vivo. [77] It was suggested that a plasma CIC discovered that LDL in these complexes had
enzyme called trans-sialidase is the possible cause of atherogenic modifications, particularly LDL were small
LDL desialylation in blood plasma. [78] dense and had decreased sialic acid content. LDL-CIC
stimulated lipid accumulation in cultured cells unlike
DESIALYLATION AND IMMUNE RESPONSE nLDL. [86] Recent studies showed that IgG and LDL-
CIC removal from patient sera reduced its atherogenic
Sialic acids belong to a group of N- or O- derivatives activity. [83] Level of LDL-CIC is used in diagnosis,
of neuraminic acid. N-acetylneuraminic acid prognosis and in several therapeutic approaches in
(Neu5AC) is the most common type found in humans. CVD patients. [14,83,84]
Neu5AC is typically found at the terminal position of
ganglioside glycan chains in the cellular glycocalyx. CONCLUSION
Sialic acids are involved in cell-cell interactions,
including those between immune cells. Neu5AC refers Sialic acid level is decreased in atherogenic LDL
and negatively correlates with triglyceride and
to a self-associated molecular patterns (SAMPs) cholesterol level in LDL. Desialylated LDL are small,
group because of their ability to suppress innate dense and highly susceptible to peroxidation in
and adaptive autoimmune response. [79] Sialic-acid- several hyperlipidemia types. Desialylation results in
binding immunoglobulin-like lectins (Siglecs) form atherogenic changes because of increased cholesterol
a group of immune cell receptors that participate intake in macrophages and smooth-muscle cells and
in the discrimination of “self” and “non-self” through is also associated with other pathologies, such as
recognition of cell glycan ligands. Macrophages have diabetes mellitus.
sialoadhesin (CD169), so-called Siglec-1, and B-cells
have CD22, so-called Siglec-2. Studies on human DECLARATIONS
immune cells discovered 14 members of the Siglec
family. Siglec receptor binding with host-specific sialic Authors’ contributions
acid provides negative regulation or even apoptosis in Analysis of literature, writing a draft: V.I. Alipov
immune cells. For example, in B-cells activation of CD22 Editing, writing a draft: V.N. Sukhorukov
pathway leads to activation of Src homology region Table and figures: V.P. Karagodin
2 domain-containing phosphatase-1 (SHP-1), which Consultation: A.V. Grechko
suppresses the activation of B-cell receptor (BCR). [80] English improvement: A.N. Orekhov
Recent study showed that sialic acid binding domain
mutations of Siglec-G resulted in decreased B-cell Financial support and sponsorship
activation threshold. [81] Dysfunction of Siglec receptor
interactions with sialic acid is associated with various This work was supported by Russian Science
autoimmune diseases. [79,80] Lack of sialoadhesin in Foundation (Grant # 14-15-00112).
macrophages causes activation of scavenger receptors Conflicts of interest
and phagocytosis. [79-82] In atherosclerosis, decreased
sialic acid content in desialylated LDL might result in The authors declare that they have no competing
increased cholesterol intake and inflammation through interests.
macrophage and B-cell activation.
Patient consent
Patients with various CVD have antibodies against Not applicable.
112 Vessel Plus ¦ Volume 1 ¦ September 26, 2017