Modulation of inflammatory mediators and pparγand nfκb expression by pravastatin in response to lipoproteins in human monocytes in vitro

Zelvyté, Inga; Dominaitiene, Ruta; Crisby, Milita; Janciauskiene, Sabina

doi:10.1006/phrs.2001.0922

Cited by 145 publications

(85 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Veh, Vehicle. Delbosc et al, 2002;Zelvyte et al, 2002) in both vascular and myeloid-lineage cells. The efficacy of this class of drugs as antiinflammatory agents in the CNS has been convincingly demonstrated in a murine model of experimental allergic encephalitis (Youssef et al, 2002;Nath et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Statins also exhibit robust anti-inflammatory effects (Pahan et al, 1997;Bellosta et al, 1998;Ortego et al, 1999;Grip et al, 2000Grip et al, , 2002Wong et al, 2001;Delbosc et al, 2002;Youssef et al, 2002;Zelvyte et al, 2002;Nath et al, 2004). Many of the antiinflammatory actions of statins are postulated to arise from a reduction of isoprenoid intermediates in the cholesterol biosynthetic pathway (Liao and Laufs, 2004).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

Cordle¹,

Landreth²

2005

J. Neurosci.

161

109

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar ␤-amyloid (A␤) in the brain, a fulminant microglialmediated inflammatory reaction, and neuronal death. The use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) is associated with a reduced risk of AD, which has been attributed to the cholesterol-lowering actions of these drugs. Statins have been reported recently to have anti-inflammatory actions in addition to their classic lipid-lowering effects. We report that statins robustly inhibited the A␤-stimulated expression of interleukin-1␤ and inducible nitric oxide synthase and the production of nitric oxide by microglia and monocytes. Statin treatment also blocked the rac1-dependent activation of NADPH oxidase and superoxide production. The anti-inflammatory actions of the statins were attributable to their ability to reduce the levels of isoprenyl intermediates in the cholesterol biosynthetic pathway. The effect of statins could not be reversed by exogenous cholesterol supplementation, indicating that the anti-inflammatory actions are distinct from their cholesterol-lowering actions. The addition of the isoprenyl precursors, mevalonic acid, and geranylgeranyl pyrophosphate (GGpp) attenuated the statin-mediated downregulation of inflammatory markers. Prevention of protein isoprenylation by the GGpp transferase inhibitor (GGTI-286) or inhibition of Rho-family function with Clostridium difficile Toxin A blocked the inflammatory response similar to the effect of statin treatment. We argue that the statin-mediated decrease in AD risk arises from their pleiotropic actions, effecting a reduction in neuronal A␤ production and microglia-directed inflammation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

Cordle¹,

Landreth²

2005

J. Neurosci.

161

109

View full text Add to dashboard Cite

show abstract

“…Simvastatin inhibits in a time-and dose-dependent way the TNFa-induced upregulation of ICAM and VCAM-1 in HUVECs by reducing NF-jB activation; this leads to reduced monocyte-EC interactions (123). Importantly, in vitro exposure of human monocytes to pravastatin abrogates LDL-induced activation of NF-jB and subsequent expression of inflammatory mediators (124). In addition, atorvastatin inhibits IL-18-induced migration of aortic VSMCs through AP-1 and NF-jB inactivation (21).…”

Section: Fig 7 Effects Of Statins On Nadph Oxidase In Ec Statins Smentioning

confidence: 99%

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Margaritis

Channon

Antoniades

2014

Antioxidants & Redox Signaling

116

View full text Add to dashboard Cite

Significance: Endothelial dysfunction and the imbalance between nitric oxide (NO) and reactive oxygen species production in the vascular endothelium are important early steps in atherogenesis, a major socioeconomic health problem. Statins have well-established roles in primary and secondary prevention of cardiovascular disease (CVD), due to both their lipid-lowering capacity and their pleiotropic properties. It is therefore important to understand the mechanisms by which statins can modify endothelial function and affect atherogenesis. Recent Advances: In the last decade, the concept of statin pleiotropy has been reinforced by a large number of cell culture, animal, and translational studies. Statins have been shown to suppress the activity of pro-oxidant enzymes (such as NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium. At the same time, they enhance endothelial NO synthase expression and activity while they also improve its enzymatic coupling. This leads to increased NO bioavailability and improved endothelial function. Critical Issues: Despite significant recent advances, the exact mechanisms of statin pleitropy are still only partially understood. The vast majority of the published literature relies on animal studies, while the actual mechanistic studies in humans are limited. Future Directions: The success of statins as endothelium redox-modifying agents with a direct impact on clinical outcome highlights the importance of the endothelium as a therapeutic target in CVD. Better understanding of the mechanisms that underlie endothelial dysfunction could lead to the design of novel therapeutic strategies that target the vascular endothelium for the prevention and treatment of CVD. Antioxid. Redox Signal. 20, 1198Signal. 20, -1215

show abstract

“…PPARs are intracellular, ligandactivated transcription factors that interfere with NF-B transcriptional activity (98)(99)(100). In vitro, statins induce the expression of PPAR␣ and PPAR␥ mRNA and protein in stimulated ECs, macrophages, and hepatocytes (80,101,102). Statin-induced PPAR up-regulation is reversed by mevalonate and GGPP, but not by squalene, which implies a Rho target (80,101).…”

Section: Statins As Antiinflammatory Drugs: Effects On Cells and Tissuesmentioning

confidence: 99%

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Abeles

Pillinger

2006

Arthritis & Rheumatism

135

View full text Add to dashboard Cite

Modulation of inflammatory mediators and pparγand nfκb expression by pravastatin in response to lipoproteins in human monocytes in vitro

Cited by 145 publications

References 40 publications

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate β-Amyloid-Induced Microglial Inflammatory Responses

Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Contact Info

Product

Resources

About