Statins and Pulmonary Fibrosis The Potential Role of NLRP3 Inflammasome Activation

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dc.contributor.authorXu, Jin-Fu
dc.contributor.authorWashko, George R.
dc.contributor.authorNakahira, Kiichi
dc.contributor.authorHatabu, Hiroto
dc.contributor.authorPatel, Avignat S.
dc.contributor.authorFernandez, Isis E.
dc.contributor.authorNishino, Mizuki
dc.contributor.authorOkajima, Yuka
dc.contributor.authorYamashiro, Tsuneo
dc.contributor.authorRoss, James C.
dc.contributor.authorEstepar, Raul San Jose
dc.contributor.authorDiaz, Alejandro A.
dc.contributor.authorLi, Hui-Ping
dc.contributor.authorQu, Jie-Ming
dc.contributor.authorHimes, Blanca E.
dc.contributor.authorCome, Carolyn E.
dc.contributor.authorD'Aco, Katherine
dc.contributor.authorMartinez, Fernando J.
dc.contributor.authorHan, MeiLan K.
dc.contributor.authorLynch, David A.
dc.contributor.authorCrapo, James D.
dc.contributor.authorMorse, Danielle
dc.contributor.authorRyter, Stefan W.
dc.contributor.authorSilverman, Edwin K.
dc.contributor.authorRosas, Ivan O.
dc.contributor.authorChoi, Augustine M. K.
dc.contributor.authorHunninghake, Gary M.
dc.date.accessioned2025-01-20T23:59:16Z
dc.date.available2025-01-20T23:59:16Z
dc.date.issued2012
dc.description.abstractRationale: The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the development or progression of interstitial lung disease (ILD) is controversial.
dc.description.abstractObjectives: To evaluate the association between statin use and ILD.
dc.description.abstractMethods: We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene. Next, we evaluated the effect of statin pretreatment: on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro.
dc.description.abstractMeasurements and Main Results: In COPDGene, 38% of subjects with ILA were taking statins compared with 27% of subjects without ILA. Statin use was positively associated in ILA (odds ratio, 1.60; 95% confidence interval, 1.03-2.50; P = 0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate that statin administration aggravates lung injury and fibrosis in bleomycin-treated mice. Statin pretreatment enhances caspase-l-mediated immune responses in vivo and in vitro; the latter responses were abolished in bone marrow-derived macrophages isolated from Nlrp3(-/-) and Casp1(-/-) mice. Finally, we provide further insights by demonstrating that statins enhance NLRP3-inflammasome activation by increasing mitochondrial reactive oxygen species generation in macrophages.
dc.description.abstractConclusions: Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation. Our findings suggest that statins may influence the susceptibility to, or progression of, ILD. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
dc.fuente.origenWOS
dc.identifier.doi10.1164/rccm.201108-1574OC
dc.identifier.eissn1535-4970
dc.identifier.issn1073-449X
dc.identifier.urihttps://doi.org/10.1164/rccm.201108-1574OC
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/95288
dc.identifier.wosidWOS:000300858400015
dc.issue.numero5
dc.language.isoen
dc.pagina.final556
dc.pagina.inicio547
dc.revistaAmerican journal of respiratory and critical care medicine
dc.rightsacceso restringido
dc.subjectstatins
dc.subjectinterstitial lung disease
dc.subjectpulmonary fibrosis
dc.subjectinflammasome
dc.subjectmitochondrial reactive oxygen species
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleStatins and Pulmonary Fibrosis The Potential Role of NLRP3 Inflammasome Activation
dc.typeartículo
dc.volumen185
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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