Parallels between the extracellular matrix roles in developmental biology and cancer biology.

Interaction of a tumor with its microenvironment is an emerging field of investigation, and the crosstalk between cancer cells and the extracellular matrix is of particular interest, since cancer patients with abundant and stiff extracellular matrices display a poorer prognosis. At the post-juvenile stage, the extracellular matrix plays predominantly a structural role by providing support to cells and tissues; however, during development, matrix proteins exert a plethora of diverse signals to guide the movement and determine the fate of pluripotent cells. Taking a closer look at the communication between the extracellular matrix and cells of a developing body may bring new insights into cancer biology and identify cancer weaknesses. This review discusses parallels between the extracellular matrix roles during development and tumor growth.

Redefining cancer research for therapeutic breakthroughs.

Cancer research has played a pivotal role in improving patient outcomes. However, despite the significant investment in fundamental cancer research over the past few decades, the translation of funding into substantial advancements in cancer treatment has been limited. This perspective article employs a detailed analysis to outline strategies for promoting innovation and facilitating discoveries within the field of cancer research.

Critical functions of extracellular matrix in brain metastasis seeding.

Human brain is characterized by extremely sparse extracellular matrix (ECM). Despite its low abundance, the significance of brain ECM in both physiological and pathological conditions should not be underestimated. Brain metastasis is a serious complication of cancer, and recent findings highlighted the contribution of ECM in brain metastasis development. In this review, we provide a comprehensive outlook on how ECM proteins promote brain metastasis seeding. In particular, we discuss (1) disruption of the blood-brain barrier in brain metastasis; (2) role of ECM in modulating brain metastasis dormancy; (3) regulation of brain metastasis seeding by ECM-activated integrin signaling; (4) functions of brain-specific ECM protein reelin in brain metastasis. Lastly, we consider the possibility of targeting ECM for brain metastasis management.

Calciprotein Particles: Balancing Mineral Homeostasis and Vascular Pathology.

[Figure: see text].

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Development of calcific aortic valve disease: Do we know enough for new clinical trials?

Calcific aortic valve disease (CAVD), previously thought to represent a passive degeneration of the valvular extracellular matrix (VECM), is now regarded as an intricate multistage disorder with sequential yet intertangled and interacting underlying processes. Endothelial dysfunction and injury, initiated by disturbed blood flow and metabolic disorders, lead to the deposition of low-density lipoprotein cholesterol in the VECM further provoking macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines. Such changes in the valvular homeostasis induce differentiation of normally quiescent valvular interstitial cells (VICs) into synthetically active myofibroblasts producing excessive quantities of the VECM and proteins responsible for its remodeling. As a result of constantly ongoing degradation and re-deposition, VECM becomes disorganised and rigid, additionally potentiating myofibroblastic differentiation of VICs and worsening adaptation of the valve to the blood flow. Moreover, disrupted and excessively vascularised VECM is susceptible to the dystrophic calcification caused by calcium and phosphate precipitating on damaged collagen fibers and concurrently accompanied by osteogenic differentiation of VICs. Being combined, passive calcification and biomineralisation synergistically induce ossification of the aortic valve ultimately resulting in its mechanical incompetence requiring surgical replacement. Unfortunately, multiple attempts have failed to find an efficient conservative treatment of CAVD; however, therapeutic regimens and clinical settings have also been far from the optimal. In this review, we focused on interactions and transitions between aforementioned mechanisms demarcating ascending stages of CAVD, suggesting a predisposing condition (bicuspid aortic valve) and drug combination (lipid-lowering drugs combined with angiotensin II antagonists and cytokine inhibitors) for the further testing in both preclinical and clinical trials.

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases.

Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the ECM from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of proteins upregulated in the ECM significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the ECM component. One of the proteins upregulated in liver metastatic ECM, annexin A1, was not previously studied in the context of cancer-associated matrisome. Here, we show that annexin A1 was markedly upregulated in colon cancer cell lines compared with cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes annexin A1 as a putative target for this disease.NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine colorectal cancer liver metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or biomarkers of hepatic metastases.

Shear stress: An essential driver of endothelial progenitor cells.

The blood flow through vessels produces a tangential, or shear, stress sensed by their innermost layer (i.e., endothelium) and representing a major hemodynamic force. In humans, endothelial repair and blood vessel formation are mainly performed by circulating endothelial progenitor cells (EPCs) characterized by a considerable expression of vascular endothelial growth factor receptor 2 (VEGFR2), CD34, and CD133, pronounced tube formation activity in vitro, and strong reendothelialization or neovascularization capacity in vivo. EPCs have been proposed as a promising agent to induce reendothelialization of injured arteries, neovascularization of ischemic tissues, and endothelialization or vascularization of bioartificial constructs. A number of preconditioning approaches have been suggested to improve the regenerative potential of EPCs, including the use of biophysical stimuli such as shear stress. However, in spite of well-defined influence of shear stress on mature endothelial cells (ECs), articles summarizing how it affects EPCs are lacking. Here we discuss the impact of shear stress on homing, paracrine effects, and differentiation of EPCs. Unidirectional laminar shear stress significantly promotes homing of circulating EPCs to endothelial injury sites, induces anti-thrombotic and anti-atherosclerotic phenotype of EPCs, increases their capability to form capillary-like tubes in vitro, and enhances differentiation of EPCs into mature ECs in a dose-dependent manner. These effects are mediated by VEGFR2, Tie2, Notch, and ß1/3 integrin signaling and can be abrogated by means of complementary siRNA/shRNA or selective pharmacological inhibitors of the respective proteins. Although the testing of sheared EPCs for vascular tissue engineering or regenerative medicine applications is still an unaccomplished task, favorable effects of unidirectional laminar shear stress on EPCs suggest its usefulness for their preconditioning.

A core matrisome gene signature predicts cancer outcome.

BACKGROUND: Accumulating evidence implicates the tumour stroma as an important determinant of cancer progression but the protein constituents relevant for this effect are unknown. Here we utilised a bioinformatics approach to identify an extracellular matrix (ECM) gene signature overexpressed in multiple cancer types and strongly predictive of adverse outcome. METHODS: Gene expression levels in cancers were determined using Oncomine. Geneset enrichment analysis was performed using the Broad Institute desktop application. Survival analysis was performed using KM plotter. Survival data were generated from publically available genesets. RESULTS: We analysed ECM genes significantly upregulated across a large cohort of patients with ovarian, lung, gastric and colon cancers and defined a signature of nine commonly upregulated genes. Each of these nine genes was considerably overexpressed in all the cancers studied, and cumulatively, their expression was associated with poor prognosis across all data sets. Further, the gene signature expression was associated with enrichment of genes governing processes linked to poor prognosis, such as EMT, angiogenesis, hypoxia, and inflammation. CONCLUSIONS: Here we identify a nine-gene ECM signature, which strongly predicts outcome across multiple cancer types and can be used for prognostication after validation in prospective cancer cohorts.

Neutrophils promote hepatic metastasis growth through fibroblast growth factor 2-dependent angiogenesis in mice.

Hepatic metastases are amenable to ablation; however, many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both protumor and antitumor effects. Here, neutrophils promoted the growth of hepatic metastases, given that depletion of neutrophils in already established, experimental, murine liver metastases led to diminished metastatic growth. Decreased growth was associated with reductions in vascular density and branching suggestive of vessel normalization. Metastasis-associated neutrophils expressed substantially more fibroblast growth factor 2 (FGF2) than naïve neutrophils, indicating neutrophil polarization by the tumor microenvironment. Administration of FGF2 neutralizing antibody to mice bearing experimental liver metastases phenocopied neutrophil depletion by reducing liver metastatic colony growth, vascular density, and branching. CONCLUSION: Here, we show, using FGF2 as an example, that identification of factors responsible for the protumoral effects of infiltrating myeloid cells can be used to target established liver metastases. Such therapies could be utilized to limit disease progression and potentiate the effects of standard ablative therapies. (Hepatology 2017;65:1920-1935).

Association of DNA repair gene polymorphisms with genotoxic stress in underground coal miners.

In underground coal mining, numerous harmful substances and ionising radiation pose a major threat to the occupational safety and health of workers. Because cell DNA repair machinery eliminates genotoxic stress conferred by these agents, we examined whether single nucleotide polymorphisms in hOGG1 (rs1052133), XRCC1 (rs25487), ADPRT (rs1136410), XRCC4 (rs6869366) and LIG4 (rs1805388) genes modulate the genotoxic damage assessed by the cytokinesis-block micronucleus assay in lymphocytes from 143 underground coal miners and 127 healthy non-exposed males. We also analyzed models of gene-gene interactions associated with increased cytogenetic damage in coal miners and determined 'protective' and 'risk' combinations of alleles. We showed that miners with the G/G genotype of the hOGG1 (rs1052133) gene had a significantly increased frequency of binucleated lymphocytes with micronuclei (13.17‰, 95% CI = 10.78-15.56) compared to the C/C genotype carriers (10.35‰, 95% CI = 9.59-11.18). In addition, in the exposed group this indicator was significantly increased in carriers of the T/T genotype of the LIG4 (rs1805388) gene compared to miners harbouring the C/T genotype (13.00‰, 95% CI = 10.96-15.04 and 9.69‰, 95% CI = 8.32-11.06, respectively). Using the multifactor dimensionality reduction method, we found the three-locus model of gene-gene interactions hOGG1 (rs1052133) × ADPRT (rs1136410) × XRCC4 (rs6869366) associated with high genotoxic risk in coal miners. These results indicate that the studied polymorphisms and their combinations are associated with cytogenetic status in miners and may be used as molecular predictors of occupational risks in underground coal mines.

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis.

Infective endocarditis (IE) is a septic inflammation of the endocardium. Recognition of microbial patterns, cytokine and acute phase responses, hemostasis features, and alterations in plasma lipid and calcium profile all have been reported to affect pathogenesis and clinical course of IE. Having recruited 123 patients with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors, we profiled their genomic DNA for 35 functionally significant polymorphisms within the 22 selected genes involved in the abovementioned pathways, with the further genetic association analysis. We found that the G/A genotype of the rs1143634 polymorphism within the IL1B gene, the G/T genotype of the rs3212227 polymorphism within the IL12B gene, the A/G genotype of the rs1130864 polymorphism within the CRP gene, and the G allele of the rs1801197 polymorphism within the CALCR gene were associated with a decreased risk of IE whereas the T/T genotype of the rs1205 polymorphism within the CRP gene was associated with a higher risk of IE. Furthermore, heterozygous genotypes of the rs1143634 and rs3212227 polymorphisms were associated with the higher plasma levels of IL-1ß and IL-12, respectively. Our results indicate that inherited variation in the cytokine, acute phase response, and calcium metabolism pathways may be linked to IE.

A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.

An association between single nucleotide polymorphisms within TLR and TREM-1 genes and infective endocarditis.

Infective endocarditis (IE) is an inflammatory condition of the lining of the heart chambers and valves, which is generally caused by bacteria. Toll-like receptors (TLRs) and Triggering receptor expressed on myeloid cells (TREMs) are key effectors of the innate system that play a significant role in the recognition of infectious agents, particularly, bacteria. We hypothesised that inherited variation in TLR and TREM-1 genes may affect individual susceptibility to IE. The distribution of genotypes and alleles of the TLR1 (rs5743551, rs5743611), TLR2 (rs3804099, rs5743708), TLR4 (rs4986790, rs4986791), TLR6 (rs3775073, rs5743810), and TREM-1 (rs1817537, rs3804277, rs6910730, rs7768162, rs2234246, rs4711668, rs9471535, rs2234237) gene polymorphisms was investigated in 110 Caucasian (Russian) subjects with IE and 300 age-, sex-, and ethnicity-matched healthy blood donors. Odds ratios with 95% confidence intervals were calculated. We found that C/C genotype of the rs3775073 polymorphism within TLR6 gene was associated with a decreased risk of IE (OR=0.51, 95% CI=0.26-0.97, P=0.032) according to the recessive model; however, we observed no association between the other investigated SNPs within TLR and TREM-1 genes and IE. Further in-depth investigations in this field are necessary to shed the light on the impact of inherited variation within innate immune response genes on the development of IE.

Correlation between genetic polymorphisms within IL-1B and TLR4 genes and cancer risk in a Russian population: a case-control study.

In the last decade, a growing interest has been devoted to the evaluation of the impact of single nucleotide polymorphisms (SNP) on cancer risk. According to the results of multiple studies, among the genes that have a considerable influence on cancer risk are those encoding pattern recognition receptors, cytokines, and antioxidant defense enzymes. Nonetheless, the effect of numerous SNPs within these genes on cancer risk has been scarcely investigated. A case-control study of 401 cases and 300 sex- and age-matched controls was performed in order to explore the role of IL1B_1473G/C (rs1143623), SOD1_7958A/G (rs4998557), TLR4_1196C/T (rs4986791), IL10_1082A/G (rs1800896), IL17A_197G/A (rs2275913), and TLR4_896A/G (rs4986790) polymorphisms in the susceptibility to colorectal cancer (n = 244), gastric carcinoma (n = 72), and ovarian cancer (n = 85). The analysis revealed a significant relationship between the presence of heterozygous genotypes for IL1B_1473G/C and TLR4_896A/G polymorphisms and higher risk of rectal cancer (codominant model, OR = 1.67; 95% CI, 1.06-2.63; p = 0.048 and OR = 2.25; 95% CI, 1.26-4.02; p = 0.014, respectively). In addition, the variant G/G genotype of the IL10_1082A/G SNP was associated with a 2.5-fold increase in ovarian cancer risk with a borderline significance (codominant model, OR = 2.45; 95% CI, 1.14-5.25; p = 0.069). Similarly, the carriers of the C/T genotype for the TLR4_1196C/T polymorphism were more susceptible to rectal cancer with a borderline significance (codominant model, OR = 1.42; 95% CI, 0.80-2.51 p = 0.06). No statistically significant associations were found when stratifying the sample by subgroups of age, sex, and clinicopathological characteristics. Finally, we observed six combinations of haplotypes for the examined SNPs, each of which either profoundly increased or decreased cancer risk. The results from our study provided evidence that IL1B_1473G/C and TLR4_896A/G SNPs are implicated in rectal cancer development in a Russian population. Further research should be addressed to clarify the role of the abovementioned polymorphisms in cancer etiology.

Genetic predisposition to calcific aortic stenosis and mitral annular calcification.

Valvular calcification precedes the development of valvular stenosis and may represent an important early phenotype for valvular heart disease. It is known that development of valvular calcification is likely to occur among members of a family. However, the knowledge about the role of genomic predictive markers in valvular calcification is still elusive. Aims of this review are to assess the impact of gene polymorphisms on risk and severity of aortic stenosis and mitral annular calcification. According to the results of the investigations carried out, all polymorphisms may be divided into the three groups conferring the level of evidence of their association with valvular stenosis. It is possible to conclude that apoB (XbaI, rs1042031, and rs6725189), ACE (rs4340), IL10 (rs1800896 and rs1800872), and LPA (rs10455872) gene polymorphisms may be associated with valvular calcific stenosis with a relatively high level of evidence. A number of other polymorphisms, such as PvuII polymorphism within the ORα gene, rs1042636 polymorphism within the CaSR gene, rs3024491, rs3021094, rs1554286, and rs3024498 polymorphisms within the IL10 gene, rs662 polymorphism within the PON1 gene, rs2276288 polymorphism within the MYO7A gene, rs5194 polymorphism within the AGTR1 gene, rs2071307 polymorphism within the ELN gene, rs17659543 and rs13415097 polymorphisms within the IL1F9 gene may correlate with a risk of calcific valve stenosis with moderate level of evidence. Finally, rs1544410 polymorphism within the VDR gene, E2 and E4 alleles within the apoE gene, rs6254 polymorphism within the PTH gene, and rs1800871 polymorphism within the IL10 gene may be associated with aortic stenosis with low level of evidence.

Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition.

Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the class I major histocompatibility complex (MHC-I) and antigen-presentation pathway, which are restored by inhibiting Cdk5 genetically or pharmacologically, as evidenced by single-cell RNA sequencing and functional studies. Mechanistically, Cdk5 suppresses MHC-I expression on the cancer cell membrane through the Irf2bp1-Stat1-importin α-Nlrc5 pathway, enabling BrMs to avoid recognition by T cells. Treatment with roscovitine-a clinically applicable Cdk5 inhibitor-alone or combined with immune checkpoint inhibitors, significantly reduces BrM burden and increases tumour-infiltrating functional CD8+ lymphocytes in mice. Thus, astrocyte-induced Cdk5 overexpression endorses BrM immune evasion, whereas therapeutically targeting Cdk5 markedly improves the efficacy of immune checkpoint inhibitors and inhibits BrM growth.

Interleukin-12: clinical usage and molecular markers of cancer susceptibility.

The last decade has seen the emergence of immunomodulators as therapeutic agents in cancer treatment. Interleukins (ILs) are a category of small cell-signaling molecules that organize communication and interaction between immune cells and therefore they could be used as perfect immunomodulators. IL-12 is a promising candidate for cancer immunotherapy since it plays a major role in development of antitumor immune response. Numerous studies report that IL-12 promotes an effective destruction of cancer cells both in vivo and in vitro. In addition, IL-12 has anti-angiogenic activity and it is able to dramatically decrease tumor-supportive activities of tumor-associated macrophages. The first part of the review is devoted to immunobiology of IL-12. Signaling pathways of IL-12 as well as clinical trials of this cytokine are discussed. The second part of the review is concerned on the inherited variations in IL-12A and IL-12B genes that could modulate cancer susceptibility, and as a consequence, possess predictive, therapeutic, or prognostic significance. It is known that functional single nucleotide polymorphisms (SNPs) in IL-12A and IL-12B genes may dramatically affect on protein expression level, or alter its functions, which may lead to immune disorders, autoimmune diseases, and eventually contribute to cancer occurrence. The list of genetic polymorphisms for further investigations might include the following: IL-12B_+1188A/C (rs3212227), IL-12A_+277G/A (rs568408), IL-12A_-798T/A (rs582054), IL-12A_-504T/G (rs190533), IL-12A_-1148T/C (rs2243123), and IL-12B_+16974 A/C. Perhaps, some of these SNPs may become an attractive target for oncogenomics and possibly could be used in programs of early cancer diagnosis as well as cancer prevention in the nearest future.

Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: a review.

Modern approaches in health care are moving toward the model of "personalized medicine." Today, current research in molecular biology and medicine is focused on developing genomic markers with predictive, therapeutic, and prognostic significance. One of the most widespread and significant genomic markers is the single nucleotide polymorphism (SNP), which represents a variation in DNA sequence when a single nucleotide differs between members of a biological species or paired chromosomes in an individual. Antioxidant defense enzymes break down dangerous reactive compounds, called reactive oxygen species, and prevent DNA strand from carcinogen-specific mutations. It is well known that inherited variations in genes that encode antioxidant defense enzymes may modulate individual susceptibility to cancer. In our previous study we have determined the predictive significance of several SNPs of superoxide dismutase (SOD) and glutathione peroxidase gene families in the context of cancer risk. The present review includes a summary and discussion of the current findings evaluating the role of SNPs of the myeloperoxidase (MPO) and paraoxanase (PON) genes in cancer occurrence and development. We suggest that rs2333227 (MPO_ -463G/A) and rs854560 polymorphisms have a great predictive significance; they could probably be utilized as cancer predictors in the future. Also, we recommend further in-depth research for rs11079344 (MPO), rs8178406 (MPO), rs2243828 (MPO), rs662 (PON1), rs705379 (PON1), and PON1_304A/G polymorphisms. These SNPs may become significant cancer-associated biomarkers.

Adipokine gene expression in adipocytes isolated from different fat depots of coronary artery disease patients.

To compare DPP4, LCN2, NAMPT, ITLN1, APLN mRNA levels in adipocytes isolated from the biopsies of subcutaneous, epicardial and perivascular fat obtained from 25 patients with coronary artery disease. Gene expression signature was determined by RT-qPCR with hydrolysis probes. We found DPP4 and APLN mRNA was higher expressed only in adipocytes isolated from epicardial adipose tissue compared to the subcutaneous fat. The ITLN1 gene was overexpressed in epicardial adipose tissue compared to both subcutaneous and perivascular tissues. APLN mRNA expression was positively correlated with total and LDL cholesterol plasma level, and DPP4 mRNA expression - with VLDL cholesterol concentration. Thus, adipocytes isolated from different adipose depots are characterised by differential gene expression of adipokines. Epicardial adipose tissue is of particular interest in the context of its function, molecular and genetic mechanisms of regulation of the cardiovascular system and as a therapeutic target for correction of adipose tissue-induced effects on health.