The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

Aristoteli, Lina Panayiota; Møller, Holger Jon; Bailey, Brian P.; Moestrup, Søren K.; Kritharides, Leonard

doi:10.1016/j.atherosclerosis.2005.05.004

Cited by 131 publications

(105 citation statements)

References 32 publications

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“…17,18 A soluble form of CD163 (sCD163) of unknown function is found in serum and its concentration is elevated in sepsis, myeloid leukemia, Gaucher disease 19 and atherosclerosis. 20 Moreover, sCD163 serum concentration has been shown to increase with obesity in patients with chronic kidney disease. 21 As CD163 is known to be highly expressed on adipose tissue macrophages, it may be speculated that the CD163/ heme oxygenase-1 system is involved in obesity-driven adipose tissue inflammation with potential consequences on insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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Objective: Insulin resistance in visceral obesity is substantially driven by adipose tissue inflammation, particularly by macrophages accumulating in obese adipose tissue. In contrast, adipose tissue macrophages express the hemoglobin scavenger receptor (CD163) and heme oxygenase-1 (gene: HMOX1) that together protect from oxidative stress. Our aim was to evaluate the expression of CD163 and HMOX1 in intra-abdominal visceral (omental) and subcutaneous adipose tissue as well as circulating soluble CD163 concentrations in human obesity and its association with adipose tissue inflammation, body fat distribution and insulin resistance. Methods: CD163, HMOX1 and CD68 mRNA expression in visceral and subcutaneous adipose tissue, serum concentration of soluble CD163 in morbidly obese patients (body mass index (BMI) 440 kg m À2 ), who underwent laparoscopic surgery for gastric banding (n ¼ 20), matched for age and sex to controls (BMIo30 kg m À2 ; n ¼ 20) was analyzed. Results: CD163 expression was highly upregulated in human adipose tissue and soluble CD163 serum concentration was elevated in obese vs lean subjects. HMOX1 was upregulated in adipose tissue by obesity as well and expressed predominantly in macrophages. Although CD163 expression strictly correlated with macrophage abundance, HMOX1 was additionally upregulated within macrophages. This upregulation was significantly lower in visceral compared with subcutaneous adipose tissue. Strikingly, relative visceral adipose tissue expression of HMOX1 negatively correlated with waist-to-hip ratio and the homeostasis model assessment of insulin resistance (both P ¼ 0.024). Conclusions: Visceral obesity is associated with defective upregulation of heme oxygenase-1 in visceral adipose tissue. A lack of this antioxidative and anti-inflammatory enzyme in visceral adipose tissue could contribute to the development of insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

et al. 2009

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“…CD163, the macrophage-specific scavenger receptor for the hemoglobin-haptoglobin complex, is another candidate gene located in the Ath37 locus (Schaer 2002). A recent study by Aristoteli et al (2006) showed that the plasma levels of CD163, which previously were found to be present in human atherosclerotic lesions (Ratcliffe et al 2001), are significant predictors of coronary artery disease in humans. Although the exact role of CD163 in the pathogenesis of atherosclerosis is not known, the ability of IL-6 to increase expression of cell-surface CD163 protein (Buechler et al 2000) and to induce hemeoxygenase-1 (HO-1) mRNA expression has led to the speculation that internalization of hemoglobinhaptoglobin complex by CD163 is an initial event in production of antiinflammatory heme metabolites by HO-1 (Moestrup and Moller 2004).…”

Section: Construction Of Con6 Subcongenic Linesmentioning

confidence: 99%

Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice

Ghazalpour¹,

Wang²,

Lusis

et al. 2006

Genetics

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We previously mapped a locus on chromosome 6 with a large effect (LOD . 6) on aortic lesion size in a (C57BL/6J 3 CAST/Ei) F 2 cross and identified arachidonate 5-lipoxygenase (5LO) as a candidate gene in this region. Subsequent studies with the 5LO knockout model showed effects on atherosclerosis and aortic aneurysms. We now report detailed genetic analysis of the chromosome 6 locus. We created a panel of overlapping and reciprocal subcongenic lines from the B6.CAST Ldlr À/À chromosome 6 congenic strain (CON6.Ldlr À/À ) and analyzed aortic lesion size in different subcongenic lines. Our results revealed that there are at least two subregions, designated as Ath37 and Ath38 that affect the size of aortic lesions independently of 5LO. We also showed that homozygote 5LO null mice develop smaller atherosclerotic lesions. We conclude that the relation between the mouse chromosome 6 locus and atherosclerosis is complex and is due to at least two genes with large effects within this region. This complexity should be considered when interpreting results of knockout studies.

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“…This increased immune activation persists even in patients on ART who have achieved virological suppression and immune reconstitution with CD4 cell count >200 mm 3 [33]. Soluble CD163 (sCD163) is a monocyte-macrophage specific scavenger receptor cleaved from activated monocytes and macrophages during inflammation, and elevated levels have been associated with coronary artery disease in the general population and HIV-infected men suggesting this inflammatory and immune pathway may be involved in the pathogenesis of atherosclerosis [34,35]. Fitch et al reported that sCD163 levels were significantly higher in HIV-infected females than HIV-infected and non-infected males [26].…”

Section: Markers Of Inflammation and Immune Activationmentioning

confidence: 99%

Review of Cardiovascular Disease in HIV-Infected Women

Adekunle¹

2016

J AIDS Clin Res

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The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

Cited by 131 publications

References 32 publications

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance

Complex Inheritance of the 5-Lipoxygenase Locus Influencing Atherosclerosis in Mice

Review of Cardiovascular Disease in HIV-Infected Women

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