Inflammatory changes in perivascular adipose tissue are associated with atherosclerotic lesions in the adjacent artery and can also be used as a marker in patient workup. While adipocyte size is known to be closely related to adipose tissue dysfunction and inflammation, it has not been widely studied in perivascular adipose tissue obtained from healthy human subjects without clinical atherosclerosis. In this cross-sectional study, we addressed this issue by measuring adipocyte size and defining its relationship to cardiovascular risk factors in a healthy cohort of living kidney donors. The presence of cardiovascular risk factors was established by a standardized questionnaire, clinical measurements and body composition analyses. Adipocyte size was measured in the perivascular depot. The proportions of various macrophage subtypes were determined by flow cytometry. To confirm the results, the proportion of CD68 + macrophages was additionally assessed by immunohistochemistry. A correlation and principal component analyses were performed to explore associations. Adipocyte size in perivascular adipose tissue correlated with markers of lipid metabolism, inflammation, and glucose metabolism. Further, the positive correlation with the pro-inflammatory subpopulation of macrophages suggests a strong local effect of perivascular adipose tissue. Perivascular adipocyte size was associated with cardiovascular risk factors and markers of inflammation in a healthy cohort of living kidney donors. This further supports the local role of adipose tissue dysfunction and inflammation in early atherosclerosis development and detection.

• Keywords
• Perivascular adipose tissue, adipocyte size, cardiovascular risk factors, inflammation, macrophages,
• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipids * MeSH
• Macrophages metabolism   MeSH
• Lipid Metabolism MeSH
• Cross-Sectional Studies MeSH
• Adipose Tissue metabolism   MeSH
• Adipocytes * metabolism   cytology   MeSH
• Cell Size MeSH
• Inflammation * metabolism   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Lipids * MeSH

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.

• Keywords
• atherosclerotic plaques, comparison, flow cytometry, macrophage polarization, macrophages (subsets), non‐atherosclerotic vessels,
• Publication type
• Journal Article 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
• Atherosclerosis * pathology   metabolism   physiopathology   MeSH
• Blood Vessels pathology   physiopathology   MeSH
• Humans MeSH
• Adipose Tissue * pathology   metabolism   physiopathology   physiology   MeSH
• Inflammation * pathology   metabolism   physiopathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review 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.

• Keywords
• cholesterol, coronary heart disease mortality, diet, economy, inflammation, macrophages, n-3 fatty acids,
• Publication type
• Journal Article MeSH

Membrane cholesterol is essential for cell membrane properties, just as serum cholesterol is important for the transport of molecules between organs. This review focuses on cholesterol transport between lipoproteins and lipid rafts on the surface of macrophages. Recent studies exploring this mechanism and recognition of the central dogma-the key role of macrophages in cardiovascular disease-have led to the notion that this transport mechanism plays a major role in the pathogenesis of atherosclerosis. The exact molecular mechanism of this transport remains unclear. Future research will improve our understanding of the molecular and cellular bases of lipid raft-associated cholesterol transport.

• Keywords
• cell membrane, cholesterol, macrophages,
• MeSH
• Atherosclerosis * MeSH
• Biological Transport MeSH
• Cell Membrane chemistry   metabolism   MeSH
• Cholesterol chemistry   metabolism   MeSH
• Homeostasis MeSH
• Humans MeSH
• Lipoproteins metabolism   MeSH
• Macrophages metabolism   MeSH
• Membrane Microdomains chemistry   metabolism   MeSH
• Lipid Metabolism MeSH
• Protein Binding MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cholesterol MeSH
• Lipoproteins MeSH

Excessive LDL cholesterol concentration together with subclinical inflammation, in which macrophages play a central role, are linked pathologies. The process starts with the accumulation of macrophages in white adipose tissue and the switch of their polarization toward a pro-inflammatory phenotype. The proportion of pro-inflammatory macrophages in adipose tissue is related to the main risk predictors of cardiovascular disease. The cholesterol content of phospholipids of cell membranes seems to possess a crucial role in the regulation of membrane signal transduction and macrophage polarization. Also, different fatty acids of membrane phospholipids influence phenotypes of adipose tissue macrophages with saturated fatty acids stimulating pro-inflammatory whereas omega3 fatty acids anti-inflammatory changes. The inflammatory status of white adipose tissue, therefore, reflects not only adipose tissue volume but also adipose tissue macrophages feature. The beneficial dietary change leading to an atherogenic lipoprotein decrease may therefore synergically reduce adipose tissue driven inflammation.

• MeSH
• Atherosclerosis * metabolism   MeSH
• Humans MeSH
• Macrophages metabolism   MeSH
• Fatty Acids metabolism   MeSH
• Adipose Tissue * metabolism   MeSH
• Inflammation metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Fatty Acids 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.

• Keywords
• human, hypercholesterolemia, inflammation, macrophage polarization, statins,
• Publication type
• Journal Article 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.

• Keywords
• Atherosclerosis, adipose tissue, cytokines, endothelium, inflammation,
• MeSH
• Atherosclerosis pathology   MeSH
• Cell Adhesion physiology   MeSH
• Vascular Cell Adhesion Molecule-1 metabolism   MeSH
• Endothelium, Vascular metabolism   MeSH
• Cytokines metabolism   MeSH
• Adult MeSH
• Endothelial Cells metabolism   MeSH
• Culture Media, Conditioned pharmacology   MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• Intercellular Adhesion Molecule-1 metabolism   MeSH
• Monocytes metabolism   MeSH
• Intra-Abdominal Fat metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Vascular Cell Adhesion Molecule-1 MeSH
• Cytokines MeSH
• ICAM1 protein, human MeSH Browser
• Culture Media, Conditioned MeSH
• Intercellular Adhesion Molecule-1 MeSH