The importance of macrophage polarization through atherogenesis is established. However, most studies rely on immunohistological approaches, which have several limitations, such as precluding comprehensive phenotypic analysis. The aim of this study was to perform an alternative analysis of macrophage phenotypes in advanced human atherosclerotic plaques and compare them with their presence in non-atherosclerotic arteries. Atherosclerotic plaques from 70 individuals indicated for carotid endarterectomy, and samples of non-atherosclerotic arterial tissue (renal artery, control group) from 45 living kidney donors were processed to obtain immunocytes and incubated with antibodies (CD45, CD14, CD16, CD36, CD163, and CD206) to be analyzed by flow cytometry. Macrophages in the atherosclerotic plaques tend to express CD16 more intensively than in non-atherosclerotic arterial tissue (transient, CD16low p < 0.001, pro-inflammatory, CD16high p < 0.001), and the expression is more closely associated with CD36 expression. Both transient and pro-inflammatory macrophages are linked with the CD206-CD163+ or CD206+CD163+ phenotype in atherosclerotic plaques, while CD206-CD163- dominates within the anti-inflammatory (CD16neg) population in the control group. Interestingly, when evaluating all macrophages (regardless of CD16 expression), almost all are CD163+ in both groups, supporting the critical importance of using a combination of specific markers. Our results provide a deeper insight into macrophage subpopulations in advanced human atherosclerotic plaques compared with those in non-atherosclerotic vessels. Additionally, our data highlight the critical importance of using appropriate techniques, such as flow cytometry, allowing for simultaneous analysis of multiple markers to accurately and comprehensively characterize macrophages within the atherosclerotic plaque.

• Klíčová slova
• atherosclerotic plaques, comparison, flow cytometry, macrophage polarization, macrophages (subsets), non‐atherosclerotic vessels,
• Publikační typ
• časopisecké články MeSH

Perivascular adipose tissue (PVAT) envelops the majority of systemic vessels, providing crucial mechanical support and vessel protection. In physiological conditions, PVAT releases various bioactive molecules, contributing to the anti-inflammatory environment around neighboring vessels. However, in conditions like obesity, PVAT can exacerbate cardiovascular issues such as atherosclerosis. Communication between PVAT and nearby vessels is bidirectional, with PVAT responding dynamically to signals from the vasculature. This responsiveness positions PVAT as a promising indicator of vascular inflammation. Recently, the role of PVAT in the CVD risk prediction is also greatly discussed. The objective of this review is to summarize the current state of knowledge about the PVAT function, its role in physiologic and pathophysiologic processes and its potential in CVD risk prediction. Keywords: Perivascular adipose tissue, inflammation, atherogenesis, Fat attenuation index.

• MeSH
• ateroskleróza * patologie   metabolismus   patofyziologie   MeSH
• cévy patologie   patofyziologie   MeSH
• lidé MeSH
• tuková tkáň * patologie   metabolismus   patofyziologie   fyziologie   MeSH
• zánět * patologie   metabolismus   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The pro-inflammatory status of adipose tissue (AT) has been found to be related to reverse cholesterol transport (RCT) from peritoneal macrophages. However, this finding was made in experimental models using induced peritonitis and isolated peritoneal macrophages of animals. This experimental relationship is in agreement with RCT changes in man in two extreme situations, sepsis or cardiovascular complications. Given the above, we sought to test RTC in relationship to macrophage polarization in the visceral AT (VAT) of living kidney donors (LKDs) and the effect of conditioned media obtained from their AT. The influence of ATCM on CE capacity was first assessed in an experiment where standard plasma was used as cholesterol acceptor from [14C] cholesterol labeled THP-1. Conditioned media as a product of LKDs' incubated AT showed no effect on CE. Likewise, we did not find any effect of individual plasma of LKDs on CE when individual plasma of LKDs were used as acceptors. On the other hand, we documented an effect of LKDs' adipose cell size on CE. Our results indicate that the pro-inflammatory status of human AT is not likely induced by disrupted RCT but might be influenced by the metabolic status of LKDs' adipose tissue.

• MeSH
• cholesterol * metabolismus   MeSH
• kultivační média speciální metabolismus   farmakologie   MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• tuková tkáň * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholesterol * MeSH
• kultivační média speciální MeSH

The high mortality of coronary heart disease (CHD) among Czech men-one of the highest worldwide-began to decline in 1991 soon after the abolition of government subsidies to all foodstuffs rich in animal fat. As participants in the WHO MONICA Project, we were able to analyze the CHD risk factors just before and after this major economic change. We had previously documented that the originally subsidized prices decreased animal fat consumption and consequently non-HDL cholesterol concentrations in the population. By the early 1990s, no progress had been made in the treatment of acute myocardial infarction, statins were unavailable as was not the currently more effective antihypertensive therapy. Our recent research proved a close relationship between cholesterolemia and proinflammatory macrophages in adipose tissue and accelerated macrophage polarization with increased palmitate and palmitoleate contents in cell membrane phospholipids. By contrast, the proportion of proinflammatory macrophages decreases with increasing presence of n-3 fatty acids in the cell membrane. The combination of non-HDL cholesterol drop and a decreased proportion of proinflammatory macrophages due to replacement of alimentary fat decreased CHD mortality immediately.

• Klíčová slova
• cholesterol, coronary heart disease mortality, diet, economy, inflammation, macrophages, n-3 fatty acids,
• Publikační typ
• časopisecké články MeSH

Statins represent one of the most widely used classes of drugs in current medicine. In addition to a substantial decrease in atherogenic low density lipoprotein (LDL) particle concentrations, several large trials have documented their potent anti-inflammatory activity. Based on our preliminary data, we showed that statins are able to decrease the proportion of pro-inflammatory macrophages (CD14+16+CD36high) in visceral adipose tissue in humans. In the present study including 118 healthy individuals (living kidney donors), a very close relationship between the pro-inflammatory macrophage proportion and LDL cholesterol levels was found. This was confirmed after adjustment for the most important risk factors. The effect of statins on the proportion of pro-inflammatory macrophages was also confirmed in an experimental model of the Prague hereditary hypercholesterolemia rat. A direct anti-inflammatory effect of fluvastatin on human macrophage polarization in vitro was documented. Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.

• Klíčová slova
• human, hypercholesterolemia, inflammation, macrophage polarization, statins,
• Publikační typ
• časopisecké články MeSH

Residential macrophages in adipose tissue play a pivotal role in the development of inflammation not only within this tissue, but also affect the proinflammatory status of the whole body. Data on human adipose tissue inflammation and the role of macrophages are rather scarce. We previously documented that the proportion of proinflammatory macrophages in human adipose tissue correlates closely with non-HDL cholesterol concentrations. We hypothesized that this is due to the identical influence of diet on both parameters and decided to analyze the fatty acid spectrum in cell membrane phospholipids of the same individuals as a parameter of the diet consumed. Proinflammatory and anti-inflammatory macrophages were isolated from human adipose tissue (n = 43) and determined by flow cytometry as CD14+CD16+CD36high and CD14+CD16-CD163+, respectively. The spectrum of fatty acids in phospholipids in the cell membranes of specimens of the same adipose tissue was analyzed, and the proportion of proinflammatory macrophage increased with the proportions of palmitic and palmitoleic acids. Contrariwise, these macrophages decreased with increasing alpha-linolenic acid, total n-3 fatty acids, n-3/n-6 ratio, and eicosatetraenoic acid. A mirror picture was documented for the proportion of anti-inflammatory macrophages. The dietary score, obtained using a food frequency questionnaire, documented a positive relation to proinflammatory macrophages in individuals who consumed predominantly vegetable fat and fish, and individuals who consumed diets based on animal fat without fish and nut consumption. he present data support our hypothesis that macrophage polarization in human visceral adipose tissue is related to fatty acid metabolism, cell membrane composition, and diet consumed. It is suggested that fatty acid metabolism might participate also in inflammation and the risk of developing cardiovascular disease.

• Klíčová slova
• inflammation, macrophages, membrane, nutrition, omega-3 fatty acids,
• MeSH
• buněčná membrána chemie   MeSH
• dieta MeSH
• dospělí MeSH
• fosfolipidy chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy fyziologie   MeSH
• mastné kyseliny chemie   MeSH
• tuková tkáň cytologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfolipidy MeSH
• mastné kyseliny MeSH

Visceral adipose tissue (VAT) may play a critical role in atherosclerotic cardiovascular disease. The goal of this study was to determine the effect of human VAT-released pro‑inflammatory cytokines on monocyte adhesion to the endothelium. The cytokine effects on monocyte adhesion to the endothelial cells (ECs) were tested using adipose tissue-conditioned media (ATCM) prepared by culturing human VAT. The cytokines concentrations in ATCM, the cytokines expression and adhesion molecules in stimulated ECs were measured. The concentrations of IL-1β,TNF-α,MCP-1,IL-10,and RANTES measured in ATCM correlated positively with monocyte adhesiveness to ECs. Additionally, ATCM increased the adhesion molecules (ICAM-1, VCAM-1) gene expression. Selective inhibitors highlighted the importance of IL-1β and TNF-α in the process by a significant decrease in monocyte adhesion compared to ATCM preconditioning without inhibitors. Human VAT significantly increased monocyte adhesion to ECs. It was significantly influenced by IL-1β, TNF-α, MCP-1, IL-10, and RANTES, with IL-1β and TNF‑α having the strongest impact.

• Klíčová slova
• Atherosclerosis, adipose tissue, cytokines, endothelium, inflammation,
• MeSH
• ateroskleróza patologie   MeSH
• buněčná adheze fyziologie   MeSH
• cévní buněčněadhezivní molekula-1 metabolismus   MeSH
• cévní endotel metabolismus   MeSH
• cytokiny metabolismus   MeSH
• dospělí MeSH
• endoteliální buňky metabolismus   MeSH
• kultivační média speciální farmakologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 metabolismus   MeSH
• monocyty metabolismus   MeSH
• nitrobřišní tuk metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cévní buněčněadhezivní molekula-1 MeSH
• cytokiny MeSH
• ICAM1 protein, human MeSH Prohlížeč
• kultivační média speciální MeSH
• mezibuněčná adhezivní molekula-1 MeSH

: Worldwide, breast cancer (BC) is the most common malignancy in women, in regard to incidence and mortality. In recent years, the negative role of obesity during BC development and progression has been made abundantly clear in several studies. However, the distribution of body fat may be more important to analyze than the overall body weight. In our review of literature, we reported some key findings regarding the role of obesity in BC development, but focused more on central adiposity. Firstly, the adipose microenvironment in obese people bears many similarities with the tumor microenvironment, in respect to associated cellular composition, chronic low-grade inflammation, and high ratio of reactive oxygen species to antioxidants. Secondly, the adipose tissue functions as an endocrine organ, which in obese people produces a high level of tumor-promoting hormones, such as leptin and estrogen, and a low level of the tumor suppressor hormone, adiponectin. As follows, in BC this leads to the activation of oncogenic signaling pathways: NFκB, JAK, STAT3, AKT. Moreover, overall obesity, but especially central obesity, promotes a systemic and local low grade chronic inflammation that further stimulates the increase of tumor-promoting oxidative stress. Lastly, there is a constant exchange of information between BC cells and adipocytes, mediated especially by extracellular vesicles, and which changes the transcription profile of both cell types to an oncogenic one with the help of regulatory non-coding RNAs.

• Klíčová slova
• abdominal fat, adiponectin, breast cancer, exosomes, hormone dependency, leptin, menopause, miRNA, obesity,
• MeSH
• abdominální obezita komplikace   metabolismus   patofyziologie   MeSH
• adiponektin škodlivé účinky   metabolismus   MeSH
• estrogeny škodlivé účinky   metabolismus   MeSH
• exozom metabolismus   MeSH
• leptin imunologie   metabolismus   MeSH
• lidé MeSH
• menopauza metabolismus   MeSH
• mikro RNA metabolismus   MeSH
• nádorová transformace buněk metabolismus   MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory prsu etiologie   metabolismus   patofyziologie   MeSH
• signální transdukce genetika   MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• zánět patofyziologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• adiponektin MeSH
• estrogeny MeSH
• exozom MeSH
• leptin MeSH
• mikro RNA MeSH

BACKGROUND/OBJECTIVES: OxLDL-β2GPI complex has been suggested to have a role in the development of atherosclerosis and other inflammatory diseases. The aim of this study was to investigate the possible association of circulating oxLDL-β2GPI with obesity-induced inflammatory state of adipose tissue and related comorbidities as metabolic syndrome development. SUBJECTS/METHODS: Two cohorts of subjects were examined in the study. Cohort I: 36 women with wide range of body mass index (17-48 kg m-2) and metabolic status (with or without metabolic syndrome (MS); cohort II: 20 obese women undergoing a dietary intervention (DI) consisting of 1-month very-low-calorie diet, and 5 months of weight-stabilization period. Serum levels of oxLDL-β2GPI were measured by enzyme-linked immunosorbent assay. Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp and homeostasis model assessment of insulin resistance. mRNA expression of macrophage markers was determined in both subcutaneous (SAT) and visceral (VAT) adipose tissue in cohort I and in SAT in cohort II. RESULTS: Serum oxLDL-β2GPI levels were increased in obese subjects with MS compared to lean or obese without MS (obese with MS: 26.6±5.0 vs lean: 15.17±1.97, P<0.001; vs obese without MS: 16.36±2.89, P<0.05). Serum oxLDL-β2GPI correlated with MS indices (glucose, high-density lipoprotein, triglyceride and ureic acid) and with mRNA expression of macrophage markers in VAT. Weight-reducing DI decreased serum oxLDL-β2GPI levels together with lipid parameters and the mRNA expression of inflammatory markers in SAT. CONCLUSIONS: OxLDL-β2GPI seems to be an important marker of visceral adipose tissue inflammation and possibly a factor contributing to insulin resistance and metabolic syndrome development in obese patients.

• MeSH
• beta-2-glykoprotein I krev   chemie   metabolismus   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny LDL krev   chemie   metabolismus   MeSH
• metabolický syndrom krev   patofyziologie   MeSH
• multiproteinové komplexy MeSH
• obezita * krev   metabolismus   patofyziologie   MeSH
• tuková tkáň metabolismus   patofyziologie   MeSH
• zánět krev   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-2-glykoprotein I MeSH
• biologické markery MeSH
• lipoproteiny LDL MeSH
• multiproteinové komplexy MeSH
• oxidized low density lipoprotein MeSH Prohlížeč

The importance of the involvement of adipose tissue macrophage subpopulations in obesity-related disorders is well known from different animal models, but human data are scarcer. Subcutaneous (n=44) and visceral (n=52) adipose tissues of healthy living kidney donors were obtained during living donor nephrectomy. Stromal vascular fractions were isolated and analysed by flow cytometry using CD14, CD16, CD36 and CD163 antibodies. Total macrophage numbers in subcutaneous adipose tissue increased (P=0.02) with body mass index (BMI), with a similar increase seen in the proportion of phagocytic CD14+CD16+CD36high macrophages (P<0.01). On the other hand, there was an inverse correlation between anti-inflammatory CD14+CD16-CD163+ macrophages (P<0.05) and BMI. These correlations disappeared after excluding obese subjects (BMI ⩾30 kg m-2) from the analysis. Interestingly, none of these subpopulations were significantly related to BMI in visceral adipose tissue. Obesity per se is associated with distinct, highly phagocytic macrophage accumulation in human subcutaneous adipose tissue.

• MeSH
• dospělí MeSH
• fagocyty metabolismus   MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• nitrobřišní tuk metabolismus   MeSH
• obezita komplikace   metabolismus   MeSH
• podkožní tuk metabolismus   MeSH
• zánět etiologie   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH