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Nikiforov et al. Proinflammatory monocyte polarization in T2DM and CHD

Table 1: Clinical characteristics of studied groups of
patients R linear = 0.158
2
15.0
Healthy T2DM CHD
subjects patients patients
(n = 50) (n = 28) (n = 27) 12.5
Age (years) 60 (9) 62 (12) 67 (7)
Gender 25/25 11/17 20/7 HbA1c 10.0
(male/female)
HbA1c (%) 5.2 (0.3) 9.7 (2.4)* 5.0 (0.4)
Body mass 27.5 (2.2) 32.1 (4.3)* 28.2 (5.01) 7.5
2
index (kg/m )
Cholesterol 4.7 (0.5) 5.0 (1.2) 5.6 (1.0)*
(mmol/L) 5.0
Triglicerides 0.94 (0.18) 1.0 (1.8) 1.6 (0.5)*
(mmol/L)
0 200 400 600 800 1000 1200
TNFa _bas
Values listed are means (standard deviation). *Significant difference
from healthy subjects, P < 0.05. T2DM: type 2 diabetes mellitus; Figure 1: Correlation plot between HbA1c level and the monocyte
CHD: coronary heart disease basal secretion of TNF-a. TNF-a: tumor necrosis factor alpha
Table 2: Proinflammatory activation of monocytes from to healthy subjects.
T2DM and CHD patients
TNF-a (pg/mL) Such strong polarization of monocytes caused by
Basal Stimulated pro-inflammatory stimuli may be associated with the
Healthy subjects (n = 50) 270 ± 75 378 ± 92 activation of many transcription factors, particularly NF-
T2DM patients (n = 28) 750 ± 92* 1,571 ± 111* kB. Activation of NF-kB in T2DM is associated with
CHD patients (n = 27) 151 ± 70* ,# 139 ± 51* ,# hyperglycaenmia-induced mitochondrial superoxide
overproduction, leading to the development of
*Significant difference from healthy subjects, P < 0.05; #significant [4,17]
difference from T2DM patients, P < 0.05. T2DM: type 2 diabetes oxidative stress . Abundance of superoxide partially
mellitus; CHD: coronary heart disease inhibits the glycolytic enzyme, GAPDH, thus diverting
upstream metabolites from glycolysis into pathways
DISCUSSION of glucose over-utilization. This leads to increased
flux of dihydroxyacetone phosphate to diacylglycerol,
an activator of PKC, and of triose phosphates to
Diabetes mellitus is associated with a rapid development methylglyoxal, the main intracellular advanced glycation
of atherosclerosis. Previously it was demonstrated end (AGE) products precursor. In its turn, protein
that oxidative stress under hyperglycemic conditions kinase C is responsible for the activation of NF-kB [17]
promotes lipid infiltration to the vascular wall caused by contributing to improvements in adhesion of monocytes
increased oxidation of lipoproteins [12] . to the vascular wall [17,18] . Jin et al. [19] found that AGEs
not only predominantly induce macrophages to secrete
Furthermore, metabolic syndrome, which encompasses inflammatory cytokines, but also induce M1 polarization.
T2DM, is characterized by chronic systemic inflammation. Moreover, AGEs activate the RAGE/NF-kB pathway,
Mechanisms underlying these pathological processes whereas the blockade of RAGE or NF-kB can attenuate
remain unclear [13-15] . In response to the development of macrophage activation [19,20] . We also found a direct
obesity, adipocytes and endothelial cells reduce their correlation between the levels of HbA1c and TNF-α
insulin sensitivity, promoting the development of T2DM in patients with newly diagnosed diabetes [Figure 1].
and cardiovascular complications. In turn, development This observation may be associated not only with more
of hyperglycemia and hyperinsulinemia provoke oxidative severe oxidative stress in conditions of hyperglycemia,
stress and cause multiple inflammatory reactions [16] . but also with obesity in patients [21] .

Polarization of monocytes may reflect the status of On the contrary, monocytes from CHD patients
the innate immune system. We studied the ability of lacked the ability to be activated in response to pro-
circulating monocytes from patients with T2DM, CHD inflammatory stimuli. Recently, similar a phenomenon
and healthy subjects to be activated into M1 and M2 was found in patients with atherosclerosis [22] .
phenotypes in vitro. Increased levels of basal and
stimulated secretion of the pro-inflammatory cytokine, In conclusion, this study aimed to establish the cause of
TNF-α, were observed in diabetic patients, compared atherosclerosis in patients with diabetes in the context

194 Vessel Plus ¦ Volume 1 ¦ December 28, 2017