BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

• Keywords
• Acute coronary syndrome, Cholesterol, Polymorphism, Risk estimation,
• MeSH
• Acute Coronary Syndrome * genetics   MeSH
• Cholesterol MeSH
• Genetic Risk Score * MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Cholesterol 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 * metabolism   MeSH
• Culture Media, Conditioned metabolism   pharmacology   MeSH
• Humans MeSH
• Macrophages metabolism   MeSH
• Adipose Tissue * metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cholesterol * MeSH
• Culture Media, Conditioned 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