Increased expression of a scavenger receptor (CD36) in monocytes from subjects with Type 2 diabetes

Sampson, Michael J.; Davies, I. R.; S, Braschi; Ivory, Kamal; Hughes, David A.

doi:10.1016/s0021-9150(02)00421-5

Cited by 98 publications

(65 citation statements)

References 25 publications

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“…It should be noted that CD36 alteration in monocytes isolated from diabetic patients was only shown to be at the translational level [13]. It has also been shown that monocytes from diabetic patients show a significantly higher level of CD36 expression, which was not changed during further exposure to hyperglycaemic conditions [36]. In this study, we provide the first indication that CD36 is upregulated at the transcriptional level in MVECs exposed to high levels of glucose.…”

Section: Discussionmentioning

confidence: 56%

Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction

et al. 2005

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Aims/hypothesis: Hyperglycaemia-induced oxidative stress is implicated in the pathogenesis of chronic diabetic complications. Glucose-mediated oxidation of LDL may result in increased oxidative stress and vascular endothelial cell dysfunction via interaction with a cell surface scavenger receptor, CD36. In this study, we investigated the role of CD36 in cultured microvascular endothelial cells (MVECs) and in the heart by using an animal model of chronic diabetes. Methods: Cultured MVECs were subjected to varying glucose concentrations and assayed for alteration in CD36 gene expression and protein levels. To assess for oxidised LDL (ox-LDL) uptake, MVECs exposed to low and high glucose were treated with ox-LDL (80 μg/ml), a ligand for CD36. Haem oxygenase-1 (HO-1) and endothelin-1 (ET-1) induction, as well as oxidative stress were determined. The role of glucose-induced CD36 alteration in ox-LDL uptake was also assayed following post-transcriptional CD36 gene silencing. For in vivo studies, CD36 mRNA and oxidative DNA and protein damage were measured in heart tissues of 1-month-old diabetic Sprague-Dawley rats. Results: We found that glucose increased CD36 mRNA and protein levels in MVECs. High levels of glucose also augmented ox-LDL uptake, in association with increasing HO-1 and ET-1 mRNA levels. CD36 gene silencing prevented glucose-induced CD36 alteration, reduced ox-LDL uptake, and prevented HO-1 and ET-1 up-regulation. Similar to in vitro studies, diabetic heart tissues exhibited increased CD36 mRNA levels and increased oxidative DNA and protein damage. Conclusions/interpretation: Our results provide evidence that up-regulation of CD36 may have a role in increasing oxidative stress in MVECs and the heart in chronic diabetes.

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Section: Discussionmentioning

confidence: 56%

Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction

et al. 2005

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“…Interestingly, our results showed that low molecular weight hyaluronan is effective in incorporating ox-LDL, probably by increasing the expression of class B scavenger receptor (CD36). CD36 is an important scavenger receptor and many studies report the relation between atherosclerosis and CD36 and diabetes [24,25]. Some studies have shown that low molecular weight hyaluronan but not high molecular weight hyaluronan induces a variety of inflammatory factors such as TNF-α, IL-1β, MIP-1α, and MIP-1β [26,27].…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Hyaluronan Increases the Uptaking of Oxidized LDL into Monocytes

et al. 2007

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Abstract. Since accumulation and interaction of immune cells including T cells and monocytes/macrophages are involved in the processes of atherosclerosis, atherosclerosis is currently understood as an inflammatory disorder. Entrapment of extracellular matrices components such as hyaluronan by monocytes and macrophages, as well as uptake of oxidized low-density lipoprotein (ox-LDL) by these cells, plays a central role in foam cell formation and the pathogenesis of atherosclerosis. We investigated the role of CD44, the principal receptor for hyaluronic acid, and ox-LDL in scavenger receptor expression on resting monocytes prepared by counterflow centrifugal elutriation from the endothelium. Our results showed that the low-molecular weight (6.9 kDa) form of hyaluronan increased the expression of CD36 scavenger receptor; the incorporation of 125 I-labeled ox-LDL, and the transendothelial migration of monocytes, which were mediated at least in part via tyrosine kinase and the PKC pathway. Our results imply that low molecular weight hyaluronan produced in large amounts in atherosclerotic lesions induces differentiation of circulating monocytes to macrophages/foam cells and enhances the progression of atherosclerosis via the PKC pathway. Furthermore, low molecular weight hyaluronan also amplifies the migration of monocytes into inflamed atherosclerotic plaques. Thus, we propose that engagement of CD44 with low molecular weight hyaluronan is centrally involved in the inflammatory pathogenesis of athelosclerotic plaques through migration of monocytes and foamed macrophage differentiation.

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“…Thiazolidinediones, a major new class of drugs to treat diabetes, up regulate CD36 in monocytes/macrophages, adipose and muscle (Wilmsen, Ciaraldi, Carter, Reehman, Mudaliar, & Henry, 2003, Kolak, et al, 2006, Hirakata, Tozawa, Imura, & Sugiyama, 2004,Llaverias, et al, 2006, and may therefore contribute to the insulin-sensitizing effects of these drugs as a result of plasma fatty acid clearance, but also potentially to atherosclerosis and obesity in these patients. Interestingly, glucose/insulin appears to increase CD36 expression (Sampson, Davies, Braschi, Ivory, & Hughes, 2003,Griffin, et al, 2001,Chabowski, et al, 2004,Chen, Yang, Loux, Georgeson, & Harmon, 2006, and because CD36 is expressed on tissues important in fatty acid metabolism (heart, skeletal muscle, fat, and in pathological states, liver) this may imply an important role for CD36 in insulin resistance (see later). Regulation of CD36 expression can be mediated both pre-and post-transcription.…”

Section: Cd36 Regulationmentioning

confidence: 97%

CD36: Implications in cardiovascular disease

Febbraio

Silverstein

2007

The International Journal of Biochemistry & Cell Biology

213

215

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CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multifunctional receptor involved in both homeostatic and pathologic conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.

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Increased expression of a scavenger receptor (CD36) in monocytes from subjects with Type 2 diabetes

Cited by 98 publications

References 25 publications

Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction

Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction

Low Molecular Weight Hyaluronan Increases the Uptaking of Oxidized LDL into Monocytes

CD36: Implications in cardiovascular disease

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