Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/171730
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Rodríguez Vilarrupla, Aina | - |
dc.contributor.author | Laviña Siemsen, Bàrbara | - |
dc.contributor.author | García Calderó, Héctor | - |
dc.contributor.author | Russo, Lucia | - |
dc.contributor.author | Rosado Mateo, Eugenio | - |
dc.contributor.author | Roglans i Ribas, Núria | - |
dc.contributor.author | Bosch i Genover, Jaume | - |
dc.contributor.author | García Pagán, Juan Carlos | - |
dc.date.accessioned | 2020-11-03T12:05:24Z | - |
dc.date.available | 2020-11-03T12:05:24Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 0168-8278 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171730 | - |
dc.description.abstract | Background & Aims: Peroxisome proliferator-activated receptor a (PPARa) is a transcription factor activated by ligands that regulates genes related to vascular tone, oxidative stress, and fibrogenesis, pathways implicated in the development of cirrhosis and portal hypertension. This study aims at evaluating the effects of PPARa activation with fenofibrate on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4-cirrhotic rats. Methods: Mean arterial pressure (MAP), portal pressure (PP), and portal blood flow (PBF) were measured in cirrhotic rats treated with oral fenofibrate (25 mg/kg/day, n = 10) or its vehicle (n = 12) for 7 days. The liver was then perfused and dose-relaxation curves to acetylcholine (Ach) were performed. We also evaluated Sirius Red staining of liver sections, collagen-I mRNA expression, and smooth muscle actin (a-SMA) protein expression, cyclo-oxygenase-1 (COX-1) protein expression, and cGMP levels in liver homogenates, and TXB2 production in perfusates. Nitric oxide (NO) bioavailability and eNOS activation were measured in hepatic endothelial cells (HEC) isolated from cirrhotic rat livers. Results: CCl4 cirrhotic rats treated with fenofibrate had a significantly lower PP (29%) and higher MAP than those treated with vehicle. These effects were associated with a significant reduction in hepatic fibrosis and improved vasodilatory response to acetylcholine. Moreover, a reduction in COX-1 expression and TXB2 production in rats receiving fenofibrate and a significant increase in NO bioavailability in HEC with fenofibrate were observed. Conclusions: PPARa activation markedly reduced PP and liver fibrosis and improved hepatic endothelial dysfunction in cirrhotic rats, suggesting it may represent a new therapeutic strategy for portal hypertension in cirrhosis. | - |
dc.format.extent | 7 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier | - |
dc.relation.isformatof | Versió postprint del document publicat a: | - |
dc.relation.ispartof | Journal of Hepatology, 2012, vol. 56, num. 5, p. 1033-1039 | - |
dc.rights | (c) Elsevier, 2012 | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Cirrosi hepàtica | - |
dc.subject.classification | Hipertensió portal | - |
dc.subject.classification | Rates (Animals de laboratori) | - |
dc.subject.other | Hepatic cirrhosis | - |
dc.subject.other | Portal hypertension | - |
dc.subject.other | Rats as laboratory animals | - |
dc.title | PPARa activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 624187 | - |
dc.date.updated | 2020-11-03T12:05:24Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Medicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
624187.pdf | 941.24 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.