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1007/s10517-017-3860-5
608 Bulletin of Experimental Biology and Medicine, Vol. 163, No. 5, September, 2017 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
The content of adipokines, pro- and anti-inflammatory cytokines were studied in adipocytes
isolated from epicardial and subcutaneous adipose tissue of 24 coronary heart disease pa-
tients. The content of leptin and soluble leptin receptor in adipocytes of epicardial adipose
tissue was higher by 28.6 and 56.9% and the level of adiponectin was lower by 33% than in
adipocytes of the subcutaneous fat. In culture of epicardial adipocytes, the levels of proinflam-
matory cytokines TNF-α and IL-1 were higher. Subcutaneous adipose tissue adipocytes were
characterized by higher levels of anti-inflammatory cytokines IL-10 and FGF-β. In epicardial
adipocytes of coronary heart disease patients, the concentrations of leptin, TNF-α, and IL-1
were higher, while the levels of defense regulatory molecules (adiponectin, IL-10, and FGF-β)
were lower than in subcutaneous adipocytes.
Key Words: epicardial adipose tissue; subcutaneous fat; adipocytes; cytokines
The key mechanism triggering the development of cor- complications, and in some cases, with manifestation
onary heart disease (CHD) is lipid metabolism distur- of type 2 diabetes mellitus [1,5].
bances, high content of atherogenic lipid-transporting An important contributor to the development of
cholesterol forms, increased metabolic activity of the cardiovascular disease is visceral adipose tissue, partic-
adipose tissue producing adipokines and cytokines, ularly of epicardial location near the atria and coronary
initiating, in turn, the formation of atherosclerotic arteries [8]. Epicardial adipose tissue (EAT) adipocytes
plaques and thrombotic reactions in coronary arteries secrete adipokines and proinflammatory cytokines di-
[2,3]. High concentrations of leptin and proinflamma- rectly to the coronary arteries, thus provoking fulminant
tory cytokines and low concentrations of adiponectin development of atherosclerosis [13,14]. The presence
in the blood of patients with myocardial infarction of inflammatory mediators in tissues adjacent to epi-
were previously reported [5]. Adipose tissue can be cardial coronary arteries can lead to activation of vas-
the source of adipokines and cytokines, as virtually cular inflammation, induction of fibrotic changes in the
all patients present with second-third degree obesity myocardium, instability of atheromatous plaques, and
[1]. Imbalance in the leptin—adiponectin system is manifestation of acute coronary events [13]. However,
associated with unfavorable prognosis, cardiovascular the adipokine and cytokine profiles of visceral fat, spe-
cifically, of epicardial location, in CHD are less studied
1
Research Institute of Complex Problems of Cardiovascular Diseases,
than those of subcutaneous adipose tissue (SAT).
Kemerovo; 2Siberian State Medical University, Ministry of Health of We studied the levels of adipokines, pro- and anti-
the Russian Federation, Tomsk, Russia. Address for correspon- inflammatory cytokines in adipocytes isolated from
dence: o_gruzdeva@mail.ru. O. V. Gruzdeva EAT and SAT of CHD patients.
TABLE 1. Content of Adiponectin, Leptin, and Soluble Leptin Receptor in Adipocyte Cultures from EAT and SAT (Me (Q1;Q3)
1 2 3 4
p<0.05. The results were presented as the median with The decrease of its concentration in EAT was associ-
the upper and lower quartiles (Me (Q1;Q3). ated with coronary artery atherosclerosis [10]. Ac-
cording to our data, 90% patients had atherosclerotic
RESULTS involvement of two or three coronary arteries.
The levels of proinflammatory cytokines TNF-α
Visceral and subcutaneous adipocytes differed by ex- and IL-1 were higher in epicardial adipocyte culture
pression of adipocyte and cytokine genes [12]. Secre- (Table 2). Activation of the proinflammatory potential
tion of EAT and SAT adipocyte factors into culture in the ischemic myocardium zone could induce fibrous
medium was studied. The content of leptin and soluble changes in cardiomyocytes, leading to their pathologi-
leptin receptor were higher in EAT adipocytes. On day cal remodeling [4].
1 of EAT adipocyte culturing, the content of leptin and Subcutaneous adipocytes were characterized by
its receptors was 28.6 and 56.9% higher, respectively higher content of protective molecules — anti-inflam-
(Table 1). On day 2 of culturing, the differences were matory cytokine IL-10 and reparation and angiogen-
more pronounced: 45.5 and 57.3% for leptin and leptin esis stimulator FGF-β. By contrast, the content of IL-
receptors, respectively. The increase of leptin con- 10 in epicardial adipocyte culture was 60% lower on
centration could cause negative shifts in adipocytes day 1 of culturing and 50.3% lower on day 2. The
and cardiomyocytes, specifically, disorders in cellular content of FGF-β in epicardial adipocyte culture was
energy homeostasis with accumulation of free fatty 51% lower on day 1. By day 2 of culturing the con-
acid oxidation products with cytotoxic effects in the centration of FGF-β dropped by 81.7% in epicardial
cells [7]. adipocytes and by 83% in subcutaneous adipocytes.
The leptin concentration decreased during cultur- However, on day 2 of culturing the content of FGF-β
ing in the EAT adipocyte culture medium (by 21.4%) in subcutaneous adipocytes was 55.8% higher than in
and in subcutaneous fat (by 40%), which could be due epicardial adipocytes.
to poor viability of adipocytes in vitro (Table 1). Hence, EAT adipocytes in CHD differ by adipo-
In contrast to leptin, adiponectin concentration on kine and cytokine profile from SAT adipocytes. Epicar-
day 1 was 33.3% lower in epicardial adipocytes than dial adipocytes of CHD patients are characterized by
in subcutaneous cells. Adiponectin content increased marked imbalance of the adipokine status with higher
during culturing: by 33.3% in epicardial adipocytes leptin concentration and lower adiponectin level, with
and by 25% in SAT adipocytes. On day 2 of culturing, predominating proinflammatory cytokines and deficit
the level of adiponectin was still lower in epicardial of anti-inflammatory IL-10. Subcutaneous adipocytes
adipocyte culture medium. Adiponectin was characte of CHD patients release a grater amount of defense
rized by anti-inflammatory and antiatherogenic effect. regulatory molecules (adiponectin, anti-inflammatory
TABLE 2. Content of TNF-α, IL-10, IL-1, and FGF-β in Adipocyte Cultures from EAT and SAT (Me (Q1;Q3)
1 2 1 2