Degree of oxidation of low density lipoprotein affects expression of CD36 and PPARγ, but not cytokine production, by human monocyte-macrophages

Kavanagh, Ian; Symes, C.; Renaudin, Pauline; Nova, Esther; Mesa, María Dolores; Boukouvalas, George; Leake, David S.; Yaqoob, Parveen

doi:10.1016/s0021-9150(03)00148-5

Cited by 24 publications

(18 citation statements)

References 38 publications

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“…Here, we showed that LoxLDL and HoxLDL increased the expression of CD36 independently of their degree of oxidation. Our results confirm previous data from others [31] and further demonstrates that this increase occurs independently of the differentiation status of the cell: non-differentiated or differentiated THP-1 cells. These results suggest that CD36-dependent oxLDL uptake and further process of foam cell formation can start very early during atherogenesis, before differentiation of monocytes into macrophages and fatty streaks formation, and minimal modification in the LDL particle can be responsible for initiate this process.…”

Section: Discussionsupporting

confidence: 93%

Role of PPAR-gamma in the Modulation of CD36 and FcgammaRII induced by LDL with Low and High Degrees of Oxidation During the Differentiation of the Monocytic THP-1 Cell Line

Ríos¹,

Jancar²,

Melo³

et al. 2008

Cell Physiol Biochem

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Scavenger or Fcγ receptors are important for capture and clearance of modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors is not regulated by intracellular levels of cholesterol and in consequence, macrophages develop into foam cells in the arterial intima. The levels of scavenger receptor CD36 are increased in atherosclerotic lesions and there is evidence that some components of oxLDL auto-regulate the expression of this receptor. Fcγ receptor expression is increased in cardiovascular diseases but it is not known weather their expression is regulated by oxLDL. The biological properties of oxLDLs vary depending on the degree of oxidation. In the present study we investigated the effect of LDL particles showing extensive or low oxidation (HoxLDL and LoxLDL) on the expression of CD36 and FcγRII in a human monocytic cell line (THP-1), differentiated or not to macrophage, and the involvement of PPARγ. It was found that both forms of oxLDL are able to increase the expression of CD36 and FcγRII and that this effect is dependent on the degree of oxidation and of the stage of cell differentiation (monocyte or macrophage). We also showed that the increased expression of FcγRII is dependent on PPARγ whereas that of the CD36 is independent of PPARγ.

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Section: Discussionsupporting

confidence: 93%

Role of PPAR-gamma in the Modulation of CD36 and FcgammaRII induced by LDL with Low and High Degrees of Oxidation During the Differentiation of the Monocytic THP-1 Cell Line

Ríos¹,

Jancar²,

Melo³

et al. 2008

Cell Physiol Biochem

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“…AGEs upregulate CD36 gene expression in a dosedependent fashion, and they also upregulate PPAR␥ gene expression (18). The increased levels of AGEs present in poorly controlled diabetic subjects (39) could account, in large part, for the difference in CD36 gene expression between poorly controlled and well-controlled patients in the present investigation.…”

Section: Discussionmentioning

confidence: 57%

“…However, in addition to this, many of the conditions usually thought to induce activation/maturation of the monocyte/macrophage and uptake of oxLDL in the subendothelial space are present within the peripheral circulation in diabetes. First, many of the molecules associated with upregulation of the scavenger receptor, CD36, are raised in the blood in diabetes; these include oxLDL (18), advanced glycation end products (AGEs) (19), , and MCP-1 (21) [rev. in 22].…”

mentioning

confidence: 99%

Activation of Peripheral Blood CD14+ Monocytes Occurs in Diabetes

et al. 2005

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Blood levels of inflammatory markers associated with endothelial dysfunction and atherosclerosis are increased in diabetic patients; the highest levels occur in poorly controlled diabetes. We investigated the activation state of peripheral blood monocytes in diabetes with respect to scavenger receptor (CD36) expression and monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and peroxisome proliferator-activated receptors mRNA expression. CD14؉ monocytes were isolated from peripheral blood of type 1 and type 2 diabetic patients with good (HbA 1c <7.0%) or poor (>9.4%) glycemic control and a group of nondiabetic subjects. Monocytes from diabetic subjects displayed increased CD36 cell surface expression (P < 0.0005) and increased uptake of oxidized LDL (P < 0.05). Monocyte chemoattractant protein-1 gene expression was increased in monocytes from both groups of diabetic subjects (P < 0.05). Both CD68 and peroxisome proliferator-activated receptor-␥ gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects). In poorly controlled diabetes, CD14؉ monocytes are functionally activated and show some of the differentiation markers associated with macrophages. These monocytes also demonstrate an increased ability for attachment to normal endothelial cells, one of the early stages in atherogenesis. Diabetes 54:2779 -2786, 2005 I t has become clear that inflammatory processes play a major role in atherogenesis and that the endothelium is intimately involved at all stages of atheroma formation. With this has come a major change in our understanding of the function of the endothelium as a diffuse organ, involved in prevention of thrombosis and in modulation of both relaxation and contraction of the blood vessels (1,2). Raised levels of the inflammatory marker C-reactive protein (CRP) are associated with altered endothelial function and arterial stiffness in healthy individuals (3,4) and are predictive of future coronary heart disease in healthy middle-aged men (5). Views on the importance of inflammatory markers have progressed to the extent that it has been suggested by some that CRP is a stronger predictor of first cardiovascular events than LDL cholesterol (6); however, others suggest a more cautious interpretation of available data (7). In vitro studies have shown that CRP induces endothelial cells to produce the inflammatory cytokine interleukin-6 (IL-6), which, at least in part, is responsible for upregulation of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) (8). CRP also induces production of monocyte chemoattractant protein-1 (MCP-1) by both endothelial (8) and vascular smooth muscle (9) cells; MCP-1 enhances the movement of mononuclear cells into the subendothelial space.Although a great deal has been published on vessel wall stiffness and the prevalence of inflammator...

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“…Kavanagh et al 39 reported that CD36 and PPAR-␥ are differentially expressed in human monocytes in response to LDL oxidized to different degrees. Using oxLDL preparations similar to those in our study, this group established that moxLDL, but not oxLDL, enhanced DNA binding to PPAR-␥.…”

Section: Discussionmentioning

confidence: 99%

Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages

Ishii

Itoh

Ruiz

et al. 2004

Circulation Research

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379

292

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Abstract-CD36 is an important scavenger receptor mediating uptake of oxidized low-density lipoproteins (oxLDLs) and plays a key role in foam cell formation and the pathogenesis of atherosclerosis. We report the first evidence that the transcription factor Nrf2 is expressed in vascular smooth muscle cells, and demonstrate that oxLDLs cause nuclear accumulation of Nrf2 in murine macrophages, resulting in the activation of genes encoding CD36 and the stress proteins A170, heme oxygenase-1 (HO-1), and peroxiredoxin I (Prx I). 4-Hydroxy-2-nonenal (HNE), derived from lipid peroxidation, was one of the most effective activators of Nrf2. Using Nrf2-deficient macrophages, we established that Nrf2 partially regulates CD36 expression in response to oxLDLs, HNE, or the electrophilic agent diethylmaleate. In murine aortic smooth muscle cells, expressing negligible levels of CD36, both moderately and highly oxidized LDL caused only limited Nrf2 translocation and negligible increases in A170, HO-1, and Prx I expression. However, treatment of smooth muscle cells with HNE significantly enhanced nuclear accumulation of Nrf2 and increased A170, HO-1, and Prx I protein levels. Because PPAR-␥ can be activated by oxLDLs and controls expression of CD36 in macrophages, our results implicate Nrf2 as a second important transcription factor involved in the induction of the scavenger receptor CD36 and antioxidant stress genes in atherosclerosis.

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Degree of oxidation of low density lipoprotein affects expression of CD36 and PPARγ, but not cytokine production, by human monocyte-macrophages

Cited by 24 publications

References 38 publications

Role of PPAR-gamma in the Modulation of CD36 and FcgammaRII induced by LDL with Low and High Degrees of Oxidation During the Differentiation of the Monocytic THP-1 Cell Line

Role of PPAR-gamma in the Modulation of CD36 and FcgammaRII induced by LDL with Low and High Degrees of Oxidation During the Differentiation of the Monocytic THP-1 Cell Line

Activation of Peripheral Blood CD14+ Monocytes Occurs in Diabetes

Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages

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