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Sobenin et al. Desialylated LDL in diabetes

Table 4: Relative electrophoretic mobility of sialylated present study, desialylated LDL from diabetic patients
and desialylated LDL fractions was additionally examined by density, particle size,
Relative LDL mobility and electrophoretic mobility to obtain a more complete
Group
Sialylated LDL Desialylated LDL physicochemical characterization of this atherogenic
Healthy subjects 1.00 (0.07) 1.27 (0.19) LDL fraction.
Type 1 diabetic patients 1.05 (0.10) 1.55 (0.17)*
Type 2 diabetic patients 1.29 (0.21) 1.85 (0.29)* The density distribution profile of desialylated LDL from
*Significant difference from sialylated LDL, P < 0.05. LDL: low- diabetic patients differed from that of sialylated LDL,
density lipoprotein evidently owing to the presence of denser particles.
While this difference in LDL density between sialylated
DISCUSSION and desialylated LDL was also observed in non-
diabetic individuals, it was markedly distinct among
We have shown previously that blood sera taken diabetics. Desialylated LDL was also characterized by
from diabetic patients, in contrast to sera from non- diminished particle size, approximately by 1.2-fold as
diabetic individuals, can induce cholesterol deposition compared with sialylated LDL.
in cultured cells derived from uninvolved human aortic
intima, mainly because of LDL. [13] LDL particles carry It has been shown that sdLDL was characterized as
a variety of modifications, which are usually inherently highly atherogenic, and its level strongly correlated with
atherogenic, unlike native LDL. [10] The increase of cardiovascular disease risk. [15,16] The presence of sdLDL
a fraction of modified LDL can cause disruption of is claimed to be highly associated with atherosclerosis
lipid metabolism and contribute to the development development, and several studies have attempted
of atherosclerotic and metabolic diseases such as to identify the risk of ischemic atherosclerotic events
diabetes. According to Tsai et al., [30] modified LDL according to LDL subclass pattern. [15,16,18] The higher
levels were significantly higher in stroke survivors, thus prevalence of small dense LDL has been associated
attributing it as a risk factor for stroke outcome.
with cardiovascular events, acute ischemic stroke
LDL particles in humans are heterogeneous in a onset, and short-term mortality after acute ischemic
[33-36]
polysaccharide moiety, and contain a single molecule stroke. Our data demonstrate that in the blood of
of apolipoprotein B-100 per particle, and also 80-100 the same patient, there are at least two distinct forms
molecules of secondary proteins, approximately 1,500 of LDL differing by particle size and density. Obviously,
molecules of esterified and non-esterified cholesterol, the LDL pattern would strongly depend on what LDL
and a varying amount of other lipids. [31] It is possible fraction prevails in circulation.
to divide the LDL pool into two different sub-fractions
[sialylated (sialic acid-rich) LDL and desialylated The most prominent feature of desialylated LDL
(sialic acid-poor) LDL]. Such separation is possible is its ability to induce intracellular cholesterol
by using a column with RCA immobilized on CNBr- accumulation. [12,13,23,32] We have found previously
120
activated agarose. [12,21] Compared with sialylated that LDL atherogenicity in CAD patients and diabetic
LDL, desialylated LDL particles are smaller in size patients correlates negatively with sialic acid levels. [13]
and contain more oxysterols, and less phospholipids Indeed, in vitro studies have shown that desialylated
and antioxidants. [12] In terms of the ability to induce LDL treated with neuraminidase, which removes the
intracellular deposition of lipids, the desialylated LDL sialic acid residues, results in a significant increase in
fraction is atherogenic. [12,23,32] Several studies have LDL potency to induce lipid accumulation in cultured
reported an elevation of sialic acid serum levels in CHD monocyte-macrophages or intimal cells. [32] However,
patients, and also on its correlation with the severity of whether the loss of sialic acid in circulating LDL is the
the coronary lesions. [33] Diabetic patients’ LDL, by the primary reason for their atherogenicity, remains unclear.
first approach, appeared to have a decreased level of The so-called desialylated LDL is characterized by
sialic acid, and further investigations have shown that several alterations to its chemical composition and
this was due to an increased proportion of desialylated physical properties, low sialic acid level being only
LDL fraction in patients’ blood and a greater extent one attribute of a wider scope of changes including the
of its desialylation. [13,14] This LDL fraction was also density, size, and electric charge of particles. [12,18,23]
characterized by increased non-enzymatic glycation
and altered lipid composition, namely, decreased Desialylated LDL showed higher mobility on agarose gel
content of esterified cholesterol and elevated level electrophoresis, thereby indicating that this LDL fraction
of lyso-phospholipids. [13,14] Taken together, these has an elevated surface net charge, i.e. is a more
findings indicate that this LDL fraction with multiple electronegative LDL particle. [18] It is definitely known that
modifications has marked atherogenic potency. In the numerous techniques of in vitro LDL modification (e.g.

34 Vessel Plus ¦ Volume 1 ¦ March 31, 2017