Modulation of Vascular Inflammation In Vitro and In Vivo by Peroxisome Proliferator–Activated Receptor-γ Activators

Pasceri, Vincenzo; Wu, Henry; Willerson, James T.; Yeh, Edward T.H.

doi:10.1161/01.cir.101.3.235

Cited by 501 publications

(299 citation statements)

References 23 publications

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“…[6][7][8]. Consistent with these findings, certain omega 3 FA inhibited leukocyte adhesion in vivo in WT but not in PPAR␣-deficient (PPAR␣ Ϫ/Ϫ ) mice (9).…”

supporting

confidence: 68%

Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

Ziouzenkova

Perrey

Asatryan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

219

176

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“…[6][7][8]. Consistent with these findings, certain omega 3 FA inhibited leukocyte adhesion in vivo in WT but not in PPAR␣-deficient (PPAR␣ Ϫ/Ϫ ) mice (9).…”

supporting

confidence: 68%

Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

Ziouzenkova

Perrey

Asatryan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

219

176

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“…(C) Representative photographs of atherosclerosis in the aorta of apoE Ϫ͞Ϫ mice, a relevant section from an untreated apoE Ϫ͞Ϫ mouse (control), and an equivalent section of an apoE-deficient mouse after receiving GW2331 (PPAR␣͞␥ coagonist) or LG100364 (RXR agonist). production of matrix metalloproteinases (14), vascular cell adhesion molecule, and intercellular adhesion molecule (19). Furthermore, PPAR␥ agonists are reported to inhibit migration of vascular smooth muscle cells (20) as well as monocyte͞ macrophage homing (19) to atherosclerotic plaques.…”

Section: Resultsmentioning

confidence: 99%

Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor

Claudel

Leibowitz

Fiévet

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

273

175

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A common feature of many metabolic pathways is their control by retinoid X receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to the development of atherosclerosis, a disease influenced by both systemic and local factors. Here we analyzed the effects of activation of RXR and some of its heterodimers in apolipoprotein E ؊͞؊ mice, a well established animal model of atherosclerosis. An RXR agonist drastically reduced the development of atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated receptor (PPAR)␥ and a dual agonist of both PPAR␣ and PPAR␥ had moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated cholesterol efflux from macrophages from wild-type, but not from LXR␣ and ␤ double ؊͞؊, mice. Hence, activation of ABC-1-mediated cholesterol efflux by the RXR͞LXR heterodimer might contribute to the beneficial effects of rexinoids on atherosclerosis and warrant further evaluation of RXR͞LXR agonists in prevention and treatment of atherosclerosis. R etinoid X receptors (RXRs) are ubiquitously expressed nuclear receptors that heterodimerize with a number of other receptors (e.g., thyroid hormone receptor, vitamin D receptor, retinoic acid receptors, etc.; refs. 1 and 2). The elucidation of RXRs biological activity has advanced significantly through the characterization of rexinoids, high-affinity selective synthetic ligands for RXRs (1, 2). The use of rexinoids led to the demonstration that RXRs are active and permissive signaling molecules in heterodimers with the farnesol X receptor (FXR) [or bile acid receptor (BAR)], the liver X receptors (LXRs), and the peroxisome proliferatoractivated receptors (PPARs). The simultaneous activation of several permissive heterodimers underlies in part RXRs pleiotropic functions, affecting numerous receptor signaling pathways, and ranges from the control of cell proliferation, differentiation, and apoptosis (3) to the regulation of glucose and lipid metabolism (4). This pivotal role of the various permissive RXR heterodimers is in fact an emerging theme in multiple metabolic pathways. Heterodimers between RXR and PPAR␥, PPAR␣, LXR␣, and FXR͞BAR respectively inf luence glucose, triglyceride, cholesterol, and bile acid homeostasis. Dysregulation of these homeostatic control pathways can result in common metabolic disorders such as obesity, type 2 diabetes, and hyperlipidemia, which are often complicated by the development of atherosclerosis.In view of the potential implication of RXRs in various metabolic pathways implicated in atherosclerosis, we studied whether modulating the activity of these receptors or of some of their heterodimers affects the development of atherosclerosis in apolipoprotein (apo)E-deficient mice. We demonstrate here that the administration of rexinoids significantly attenuates atherosclerosis development, and we show that this effect might be linked to the activation of reverse cholesterol transpor...

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“…Here we show that PPAR␥-RXR agonists inhibit parasite-induced TNF-␣ secretion by monocytes and THP-1 cells. PPAR␥ agonists have also been shown to inhibit TNF-␣-induced ICAM-1 expression (64). Collectively, these observations have clinical implications and suggest that adjunctive therapy with PPAR␥-RXR agonists might reduce excessive or unbalanced proinflammatory responses to infection and might inhibit the up-regulation of endothelial cell receptors associated with severe malaria.…”

Section: Figurementioning

confidence: 89%

Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

Serghides

Kain

2001

The Journal of Immunology

101

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Severe and fatal malaria is associated with the failure of host defenses to control parasite replication, excessive secretion of proinflammatory cytokines such as TNF-α, and sequestration of parasitized erythrocytes (PEs) in vital organs. The identification of CD36 as a major sequestration receptor has led to the assumption that it contributes to the pathophysiology of severe malaria and has prompted the development of antiadherence therapies to disrupt the CD36-PE interaction. This concept has been challenged by unexpected evidence that individuals deficient in CD36 are more susceptible to severe and cerebral malaria. In this study, we demonstrate that CD36 is the major receptor mediating nonopsonic phagocytosis of PEs by macrophages, a clearance mechanism of potential importance in nonimmune hosts at the greatest risk of severe malaria. CD36-mediated uptake of PEs occurs via a novel pathway that does not involve thrombospondin, the vitronectin receptor, or phosphatidylserine recognition. Furthermore, we show that proliferator-activated receptor γ-retinoid X receptor agonists induce an increase in CD36-mediated phagocytosis and a decrease in parasite-induced TNF-α secretion. Specific up-regulation of monocyte/macrophage CD36 may represent a novel therapeutic strategy to prevent or treat severe malaria.

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Modulation of Vascular Inflammation In Vitro and In Vivo by Peroxisome Proliferator–Activated Receptor-γ Activators

Cited by 501 publications

References 23 publications

Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

Lipolysis of triglyceride-rich lipoproteins generates PPAR ligands: Evidence for an antiinflammatory role for lipoprotein lipase

Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor

Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

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