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

Background The risk of cardiovascular disease is closely connected to adipose tissue inflammation. The links between cardiovascular risk predictors and pro and anti-inflammatory macrophages in human adipose tissue were analysed to gain an insight into the pathophysiology of cardiovascular disease. Design Subcutaneous and visceral adipose tissues were obtained from 79 subjects, 52 living kidney donors (during nephrectomy) and 27 patients with peripheral artery disease (during arterial tree reconstruction). Methods Macrophage subsets were isolated from adipose tissues and analysed by flow cytometry using CD14, CD16, CD36 and CD163 monoclonal antibodies. The mutually adjusted differences of phagocytic pro-inflammatory (CD14 + CD16 + CD36high), anti-inflammatory (CD14 + CD16-CD163+) and transitional subsets of macrophages were analysed in relation to cardiovascular predictors (sex, age, body mass index, smoking, hypercholesterolaemia, hypertension and statin treatment). Results Age, male sex and hypercholesterolaemia were closely positively associated with the phagocytic pro-inflammatory macrophage subset in visceral adipose tissues. Interestingly, the proportion of phagocytic pro-inflammatory macrophages was relevantly decreased by statin therapy. A strong positive association of body mass index to the phagocytic pro-inflammatory subset was found in subcutaneous adipose tissues only. A minor transitional subpopulation, CD14 + CD16 + CD36lowCD163+, increased with age in both adipose tissues. This transitional subpopulation was also negatively associated with obesity and hypercholesterolaemia in visceral adipose tissues. Conclusion An effect of cardiovascular risk predictors on adipose tissue macrophage subpopulations was revealed. Interestingly, while age, male sex and hypercholesterolaemia were connected with the pro-inflammatory macrophage subpopulation in visceral adipose tissues, body mass index had a prominent effect in subcutaneous adipose tissues only. A decreasing effect of statins on these pro-inflammatory macrophages was documented.

• Klíčová slova
• Cardiovascular risk factors, adipose tissue, inflammation, macrophage, statins,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• fagocytóza MeSH
• fenotyp MeSH
• hypercholesterolemie krev   farmakoterapie   patologie   MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy účinky léků   metabolismus   patologie   MeSH
• mediátory zánětu krev   MeSH
• nitrobřišní tuk účinky léků   metabolismus   patologie   MeSH
• onemocnění periferních arterií krev   patologie   chirurgie   MeSH
• podkožní tuk účinky léků   metabolismus   patologie   MeSH
• prognóza MeSH
• rizikové faktory MeSH
• sexuální faktory MeSH
• statiny terapeutické užití   MeSH
• studie případů a kontrol MeSH
• věkové faktory 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
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• mediátory zánětu MeSH
• statiny MeSH

Data from experimental animal models and in vitro studies suggest that both hyperlipoproteinemia and obesity predispose to development of proinflammatory pathways of macrophages within adipose tissue. The aim of this study was to analyze whether non-HDL cholesterol concentration in healthy living kidney donors (LKDs) is related to the number and phenotype of proinflammatory macrophages in visceral and subcutaneous adipose tissue. Adipose tissue samples were collected by cleansing the kidney grafts of LKDs obtained peroperatively. The stromal vascular fractions of these tissues were analyzed by flow cytometry. Proinflammatory macrophages were defined as CD14+ cells coexpressing CD16+ and high-expression CD36 as well (CD14+CD16+CD36+++), while CD16 negativity and CD163 positivity identified alternatively stimulated, anti-inflammatory macrophages. Non-HDL cholesterol concentration positively correlated to proinflammatory macrophages within visceral adipose tissue, with increased strength with more precise phenotype determination. On the contrary, the proportion of alternatively stimulated macrophages correlated negatively with non-HDL cholesterol. The present study suggests a relationship of non-HDL cholesterol concentration to the number and phenotype proportion of macrophages in visceral adipose tissue of healthy humans.

• Klíčová slova
• atherosclerosis, high density lipoprotein, inflammation, macrophage/monocyte, membrane receptors,
• MeSH
• CD antigeny metabolismus   MeSH
• cholesterol metabolismus   MeSH
• dospělí MeSH
• ledviny MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy cytologie   metabolismus   MeSH
• nitrobřišní tuk cytologie   metabolismus   MeSH
• transplantace ledvin MeSH
• žijící dárci * 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
• Názvy látek
• CD antigeny MeSH
• cholesterol MeSH

BACKGROUND AND AIMS: Macrophages play important roles in adipose tissue inflammation and its consequences. Unfortunately, a detailed description of the macrophage phenotypes in different human adipose tissues is not available. SUBJECTS AND METHODS: Subcutaneous, visceral and perivascular adipose tissues were obtained from 52 living kidney donors during live donor nephrectomy. Stromal vascular fractions were isolated, and the macrophage phenotypes were analyzed by flow cytometry using surface markers (CD14, CD16, CD36, and CD163). RESULTS: In addition to CD16 positivity, pro-inflammatory macrophages also display high scavenger receptor CD36 expression. The great majority of CD16 negative macrophages express the anti-inflammatory CD163 marker. The presence of pro-inflammatory macrophages was almost twice as high in visceral (p < 0.0001) and perivascular (p < 0.0001) adipose tissues than in subcutaneous tissue. This difference was substantially more pronounced in the postmenopausal women subgroup, consequentlly, the total difference was driven by this subgroup. CONCLUSION: We obtained detailed information about M1 and M2 macrophage phenotypes in human adipose tissue. The visceral and perivascular adipose tissues had substantially higher pro-inflammatory characteristics than the subcutaneous tissue. The higher proportion of pro-inflammatory macrophages in the visceral adipose tissue of postmenopausal women might be related to an increased cardiovascular risk.

• Klíčová slova
• Adipose tissue, Inflammation, Macrophages, Menopause,
• MeSH
• dárci tkání MeSH
• fenotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy cytologie   MeSH
• nitrobřišní tuk cytologie   MeSH
• podkožní tuk cytologie   MeSH
• průtoková cytometrie MeSH
• separace buněk MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The presence of proinflammatory monocytes/macrophages (CD14+CD16+) has been documented in conditions of inflammation, such as atherosclerosis. We analysed the proportion of proinflammatory monocytes/macrophages in perirenal and perivascular fat in healthy living kidney donors with regard to sex and age reflecting reproductive status in women; therefore, women were further divided to younger and older group (younger and older than 51 years) reflecting potential age of menopause. Monocyte/macrophages were identified as CD14+ mononuclear cells and divided into subpopulations based on the co-expression of CD16. We found no differences in the monocyte/macrophage content between men (n = 15) and women (n = 28). Conversely, we observed a higher proportion of double positive CD14+CD16+ monocytes/macrophages in older women (n = 14) compared to younger women (n = 14). In addition, a strong correlation was found between the monocyte/macrophage content in fat and age only in older women. Therefore, proinflammatory monocytes/macrophages (CD14+CD16+) should be evaluated according to the sex and age.

• Klíčová slova
• Adipose tissue, Monocytes/macrophages, Reproductive status, Sex,
• MeSH
• antigeny CD14 analýza   MeSH
• biologické markery analýza   MeSH
• disparity zdravotního stavu * MeSH
• dospělí MeSH
• GPI-vázané proteiny analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   MeSH
• postmenopauza MeSH
• premenopauza MeSH
• receptory IgG analýza   MeSH
• rizikové faktory MeSH
• rozmnožování * MeSH
• senioři MeSH
• sexuální faktory MeSH
• stárnutí imunologie   MeSH
• tuková tkáň imunologie   MeSH
• věkové faktory MeSH
• zánět imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antigeny CD14 MeSH
• biologické markery MeSH
• FCGR3B protein, human MeSH Prohlížeč
• GPI-vázané proteiny MeSH
• receptory IgG MeSH