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Alipov et al. Difference between native and desialylated LDL

Currently, a high level of LDL cholesterol (LDL-C) could accumulate in endothelial cells, monocytes, and
is considered as a risk factor for CVD in clinical lymphocytes through binding to scavenger receptors,
practice, and various treatment options (e.g. statins) such as platelet-activating factor receptor (PAF), lectin-
are used to decrease it. [5,6] However, simple reduction like oxidized LDL receptors (LOX-1), and scavenger
of blood cholesterol level is not sufficient for effective receptor A (SRA). [17,18] T-lymphocyte receptors (TCR)
atherosclerosis prevention. Moreover, this approach and CD14 are also involved in conveying LDL(-)
was demonstrated not to be efficient in several clinical biological effects. [19] It’s worth mentioning that nLDL
studies. [7,8] The main drawback of statin therapy is binding with oxidized forms of hemoglobin may cause
the presence of several severe side-effects, such as changes in conformation and chemical composition of
statin-associated muscle symptoms, diabetes mellitus, nLDL apolipoproteins. [20] High intracellular lipid level and
[9]
and central nervous system disorders. During the activation of receptor pathways may result in cytotoxicity
last decade, molecular mechanisms of atherosclerosis and the release of inflammatory cytokines. [21-24] On the
have become a subject of intensive research aimed at other hand, recent studies showed that LDL(-) had
improving the clinical outcomes and developing novel an ability to induce anti-inflammatory cytokines [e.g.
therapies. interleukin-10 (IL-10)] and counteract inflammatory
effects promoted by lipopolysaccharides. [19,25] In that
MODIFIED LDL AND ATHEROSCLEROSIS regard, the atherogenic role of LDL(-) needs further
investigation. However, multiple studies confirmed that
Numerous studies have revealed that LDL subtypes high LDL(-) level was a risk factor for CVD, which might
form a heterogeneous group with different chemical be connected with other LDL(-) modifications, such as
and physical properties. Several types and subclasses desialylation and oxidation. [16,26-28]
of circulating LDL have different atherogenic effects.
According to the widely accepted classification, the Lipoprotein (a) [Lp(a)] differs from LDL only by the
following LDL subtypes can be distinguished: small presence of apoplipoprotein (a) bound to apolipoprotein
(dense), medium and large LDL. Dense LDL [with B-100 (apoB-100) via a disulfide bridge. Lp(a) is normally
density (d) 1.044-1.060 g/mL] is considered to be present in the blood, and its plasma concentrations
the most atherogenic. Particles of this LDL subtype range from 1 to 1,000 mg/dL. High levels of Lp(a) are
differ in size from 15 to 20 nm. For large LDL (d. associated with some pathologies. For instance, Lp(a)
1.019-1.034 g/mL), mean particle size is 22 nm (up level increased within 24 h after acute myocardial
to 30 nm). Medium LDL (d. 1.034-1.044 g/mL) has a infarction, and its transient increase accompanied acute
particle size in between small and large LDL. [10] An and chronic inflammatory processes. [29,30] Lp(a) gene
early study by Filipovic [11] and co-authors showed polymorphism was associated with the incidence of
that LDL modification enhanced cholesterol intake by cerebral vascular accident of large vessels, peripheral
cultured cells. Subsequently, naturally modified LDL arterial disease, and abdominal aorta aneurysm. [31]
types were found in human blood. [11,12] During the Lp(a) level also correlated with IL-6, tumor necrosis
past decades, numerous studies confirmed that LDL factor alpha (TNF-α), transforming growth factor
modifications, such as oxidation, desialylation and beta (TGF-β), and monocyte chemoattractant protein
enzymatic processing, play a key role in increasing (MCP-1) levels. [32] In Korean population, patients with
cholesterol intake, and the level of multiple modified high Lp(a) level had higher CVD risk and worse disease
LDL correlates with the risk of CVD. [13,14] course. [33] A Danish prospective study of 9,000 subjects
revealed that extremely high plasma Lp(a) level (over
Other types of lipoproteins that are distinguished in 120 mg/dL) increased CVD risk 4-fold. [34] On the other
some studies are electronegative LDL [LDL(-)] and hand, multiple prospective studies showed that a high
lipoprotein (a) [Lp(a)]. The former subclass includes Lp(a) level was not an independent risk factor for
modified LDL with increased negative charge, which cardiovascular or cerebrovascular diseases. [29,35]
accounts for 3-5% of the total LDL in normolipidemic
subjects. Several studies on LDL(-) showed that CHEMICAL COMPOSITION OF LDL
it represents a heterogeneous group of particles
with various chemical modifications (oxidation, Non-modified, or nLDL, particle contains apolipoprotein
glycosylation, non-esterified fatty-acid enrichment, B-100 (apoB-100) molecule, about 90 molecules of
desialylation, and enzymatic modification) that share other regulatory proteins, a phospholipid monolayer,
the common feature of increased electronegativity. and a hydrophobic core, which accounts for 75%
Electronegative LDL is characterized by an enhanced of LDL particle weight. [36] LDL contains proteins
ability to aggregate and is more susceptible to oxidation regulating apoB-100 metabolism and lipid transport
than native LDL (nLDL). [15,16] It was found that LDL(-) [apolipoprotein C-II (apoC-II), apoC-III, apoE, apoA-I,

108 Vessel Plus ¦ Volume 1 ¦ September 26, 2017