The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Acute Antiinflammatory Properties of Statins Involve Peroxisome Proliferator–Activated Receptor-α via Inhibition of the Protein Kinase C Signaling Pathway
Abstract
Statins are inhibitors of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease (CVD). In addition to their cholesterol-lowering activities, statins exert pleiotropic antiinflammatory effects, which might contribute to their beneficial effects not only on CVD but also on lipid-unrelated immune and inflammatory diseases, such as rheumatoid arthritis, asthma, stroke, and transplant rejection. However, the molecular mechanisms involved in these antiinflammatory properties of statins are unresolved. Here we show that the peroxisome proliferator–activated receptor (PPAR) α mediates antiinflammatory effects of simvastatin in vivo in models of acute inflammation. The inhibitory effects of statins on lipopolysaccharide-induced inflammatory response genes were abolished in PPARα-deficient macrophages and neutrophils. Moreover, simvastatin inhibited PPARα phosphorylation by lipopolysaccharide-activated protein kinase C (PKC) α. A constitutive active form of PKCα inhibited nuclear factor κB transrepression by PPARα whereas simvastatin enhanced transrepression activity of wild-type PPARα, but not of PPARα mutated in its PKC phosphorylation sites. These data indicate that the acute antiinflammatory effect of simvastatin occurs via PPARα by a mechanism involving inhibition of PKCα inactivation of PPARα transrepression activity.
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Cites
Mechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
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Self-citationDelerive, P., De Bosscher, K., Besnard, S., Vanden Berghe, W., Peters, J. M., Gonzalez, F. J., Fruchart, J.-C., Tedgui, A., Haegeman, G., & Staels, B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32048 · Cited by 1,089
Self-citationPeroxisome proliferator-activated receptors in inflammation control
Delerive, P., Fruchart, J., & Staels, B. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1690453 · Cited by 755
Self-citationA novel anti-inflammatory role for simvastatin in inflammatory arthritis.
Leung, B. P., Sattar, N., Crilly, A., Prach, M., McCarey, D. W., Payne, H., Madhok, R., Campbell, C., Gracie, J. A., Liew, F. Y., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.3.1524 · Cited by 434
A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma.
McKay, A., Leung, B. P., McInnes, I. B., Thomson, N. C., & Liew, F. Y. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.5.2903 · Cited by 309
p38 Mitogen-activated Protein Kinase Activates Peroxisome Proliferator-activated Receptor α
Barger, P. M., Browning, A. C., Garner, A. N., & Kelly, D. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105945200 · Cited by 260
Cited by
Periodontitis and cardiovascular diseases: Consensus report
Sanz, M., Marco del Castillo, A., Jepsen, S., Gonzalez‐Juanatey, J. R., D’Aiuto, F., Bouchard, P., Chapple, I., Dietrich, T., Gotsman, I., Graziani, F., et al. (2020) · Journal of Clinical Periodontology · doi:10.1111/jcpe.13189 · Cited by 1,482
Pleiotropic Effects of Statins on the Cardiovascular System
Oesterle, A., Laufs, U., & Liao, J. K. (2017) · Circulation Research · doi:10.1161/circresaha.116.308537 · Cited by 1,247
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Self-citationKell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
PPARα: Energy Combustion, Hypolipidemia, Inflammation and Cancer
Pyper, S. R., Viswakarma, N., Yu, S., & Reddy, J. K. (2010) · Nuclear Receptor Signaling · doi:10.1621/nrs.08002 · Cited by 379
Metadata
- Authors
- Paumelle, R., Blanquart, C., Briand, O., Barbier, O., Duhem, C., Woerly, G., Percevault, F., Fruchart, J.-C., Dombrowicz, D., Glineur, C., & Staels, B.
- Venue
- Circulation Research
- Published
- 2006-02-17
- Volume
- 98
- Issue
- 3
- Pages
- 361-369
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2143808586
- Cited by
- 165
- References
- 6
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Acute Antiinflammatory Properties of Statins Involve Peroxisome Proliferator–Activated Receptor-α via Inhibition of the Protein Kinase C Signaling Pathway. https://app.cochat.ai/papers/10.1161/01.res.0000202706.70992.95
- The paper
- Paumelle, R., Blanquart, C., Briand, O., Barbier, O., Duhem, C., Woerly, G., Percevault, F., Fruchart, J.-C., Dombrowicz, D., Glineur, C., & Staels, B. (2006). Acute Antiinflammatory Properties of Statins Involve Peroxisome Proliferator–Activated Receptor-α via Inhibition of the Protein Kinase C Signaling Pathway. Circulation Research. https://doi.org/10.1161/01.res.0000202706.70992.95
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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