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.

Laboratory for Atherosclerosis Research Centre for Experimental Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

Transplant Surgery Department Institute for Clinical and Experimental Medicine Prague Czech Republic

Zobrazit více v PubMed

Keys A., Aravanis C., Blackburn H. W., Van Buchem F. S., Buzina R., Djordjević B. D., Dontas A. S., Fidanza F., Karvonen M. J., Kimura N., et al. . 1966. Epidemiological studies related to coronary heart disease: characteristics of men aged 40–59 in seven countries. Acta Med. Scand. Suppl. 460: 1–392. PubMed

Goldstein J. L., and Brown M. S.. 1973. Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. Proc. Natl. Acad. Sci. USA. 70: 2804–2808. PubMed PMC

Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., and Hennekens C. H. H.. 1997. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 336: 973–979. PubMed

Guilherme A., Virbasius J. V. , V. Puri, and M. P. Czech. 2008. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell Biol. 9: 367–377. PubMed PMC

Blüher M. 2009. Adipose tissue dysfunction in obesity. Exp. Clin. Endocrinol. Diabetes. 117: 241–250. PubMed

Medbury H. J., Willliams H., Li S., and Fletcher J. P.. 2015. The bidirectional relationship between cholesterol and macrophage polarization. J. Clin. Cell. Immunol. 6: 1–7.

Yvan-Charvet L., Welch C., Pagler T. A., Ranalletta M., Lamkanfi M., Han S., Ishibashi M., Li R., Wang N., and Tall A. R.. 2008. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation. 118: 1837–1847. PubMed PMC

Tall A. R., and Yvan-Charvet L.. 2015. Cholesterol, inflammation and innate immunity. Nat. Rev. Immunol. 15: 104–116. PubMed PMC

Peled M., and Fisher E. A.. 2014. Dynamic aspects of macrophage polarization during atherosclerosis progression and regression. Front. Immunol. 5: 579. PubMed PMC

Subramanian S., and Chait A.. 2009. The effect of dietary cholesterol on macrophage accumulation in adipose tissue: implications for systemic inflammation and atherosclerosis. Curr. Opin. Lipidol. 20: 39–44. PubMed

Aguilar D., and Fernandez M. L.. 2014. Hypercholesterolemia induces adipose dysfunction in conditions of obesity and nonobesity. Adv. Nutr. 5: 497–502. PubMed PMC

Subramanian S., Han C. Y., Chiba T., McMillen T. S., Wang S. A., Haw A. III, Kirk E. A., O’Brien K. D., and Chait A.. 2008. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 28: 685–691. PubMed PMC

Busnelli M., Manzini S., Froio A., Vargiolu A., Cerrito M. G., Smolenski R. T., Giunti M., Cinti A., Zannoni A., Leone B. E., et al. . 2013. Diet induced mild hypercholesterolemia in pigs: local and systemic inflammation, effects on vascular injury-rescue by high-dose statin treatment. PLoS One. 8: e80588. PubMed PMC

Goossens G. H. 2008. The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94: 206–218. PubMed

Baker A. R., Silva N. F., Quinn D. W., Harte A. L., Pagano D., Bonser R. S., Kumar S., and McTernan P. G.. 2006. Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovasc. Diabetol. 5: 1. PubMed PMC

Hill A. A., Reid Bolus W., and Hasty A. H.. 2014. A decade of progress in adipose tissue macrophage biology. Immunol. Rev. 262: 134–152. PubMed PMC

Nielsen M. H., Irvine H., Vedel S., Raungaard B., Beck-Nielsen H., and Handberg A.. 2015. Elevated atherosclerosis-related gene expression, monocyte activation and microparticle-release are related to increased lipoprotein-associated oxidative stress in familial hypercholesterolemia. PLoS One 10: e0121516. PubMed PMC

Rogacev K. S., Zawada A. M., Emrich I., Seiler S., Böhm M., Fliser D., Woollard K. J., and Heine G. H.. 2014. Lower apoA1 and lower HDL-C levels are associated with higher intermediate CD14++CD16+ monocyte counts that predict cardiovascular events in chronic kidney disease. Arterioscler. Thromb. Vasc. Biol. 34: 2120–2127. PubMed

Krychtiuk K. A., Kastl S. P., Pfaffenberger S., Pongratz T., Hofbauer S. L., Wonnerth A., Katsaros K. M., Goliasch G., Gaspar L., Huber K., et al. . 2014. Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease. Atherosclerosis. 237: 589–596. PubMed PMC

Aron-Wisnewsky J., Tordjman J., Poitou C., Darakhshan F., Hugol D., Basdevant A., Aissat A., Guerre-Millo M., and Clément K.. 2009. Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J. Clin. Endocrinol. Metab. 94: 4619–4623. PubMed

Barros M. H., Hauck F., Dreyer J. H., Kempkes B., and Niedobitek G.. 2013. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages. PLoS One. 8: e80908. PubMed PMC

Králová Lesná I., Poledne R., Fronek J., Králová A., Sekerková A., Thieme F., and Pitha J.. 2015. Macrophage subsets in the adipose tissue could be modified by sex and the reproductive age of women. Atherosclerosis. 241: 255–258. PubMed

Sheedy F. J., Grebe A., Rayner K. J., Kalantari P., Ramkhelawon B., Carpenter S. B., Becker C. E., Ediriweera H. N., Mullick A. E., Golenbock D. T., et al. . 2013. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14: 812–820. PubMed PMC

Buechler C., Eisinger K., and Krautbauer S.. 2013. Diagnostic and prognostic potential of the macrophage specific receptor CD163 in inflammatory diseases. Inflamm. Allergy Drug Targets. 12: 391–402. PubMed

Cífková R., Skodová Z., Bruthans J., Adámková V., Jozífová M., Galovcová M., Wohlfahrt P., Krajcoviechová A., Poledne R., Stávek P., et al. . 2010. Longitudinal trends in major cardiovascular risk factors in the Czech population between 1985 and 2007/8. Czech MONICA and Czech post-MONICA. Atherosclerosis. 211: 676–681. PubMed

Coen P. M., Flynn M. G., Markofski M. M., Pene B. R., and Hannemann R. E.. 2010. Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population. Metabolism. 59: 1775–1783. PubMed

Fjeldborg K., Pedersen S. B., Møller H. J., Christiansen T., Bennetzen M., and Richelsen B.. 2014. Human adipose tissue macrophages are enhanced but changed to anti-inflammatory profile in obesity. J. Immunol. Res. 2014: 309548. PubMed PMC

Kralova Lesna I., Suchanek P., Kovar J., Stavek P., and Poledne R.. 2008. Replacement of dietary saturated FSAs by PUFAs in diet and reverse cholesterol transport. J. Lipid Res. 49: 2414–2418. PubMed

Kong L. C., Holmes B. A., Cotillard A., Habi-Rachedi F., Brazeilles R., Gougis S., Gausserès N., Cani P. D., Fellahi S., Bastard J. P., et al. . 2014. Dietary patterns differently associate with inflammation and gut microbiota in overweight and obese subjects. PLoS One. 9: e109434. PubMed PMC

Perivascular adipocyte size is related to the lipid profile and inflammatory changes in a healthy population

Human macrophage pro-inflammatory polarization in response to free cholesterol and cholesterol remnants

Rapid Drop in Coronary Heart Disease Mortality in Czech Male Population-What Was Actually behind It?

Adipose tissue macrophages and atherogenesis - a synergy with cholesterolaemia

Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation

Polarization of Macrophages in Human Adipose Tissue is Related to the Fatty Acid Spectrum in Membrane Phospholipids