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| Pàgina inicial > Articles > Articles publicats > Functionalized cerium oxide nanoparticles mitigate the oxidative stress and proinflammatory activity associated to the portal vein endothelium of cirrhotic rats |
(Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Institut Català de Nanociència i Nanotecnologia) (Universitat de Barcelona. Departament de Biomedicina) (Institut Català de Nanociència i Nanotecnologia) (Universitat de Barcelona. Departament de Biomedicina)
| Data: | 2019 |
| Resum: | Background and aims- The occurrence of endothelial alterations in the liver and in the splanchnic vasculature of cirrhotic patients and experimental models of liver diseases has been demonstrated. However, the pathological role of the portal vein endothelium in this clinical context is scarcely studied and, therefore, deserves attention. In this context, we aimed to investigate whether pathological endothelial activation occurs in the portal vein of cirrhotic rats. Methods- Cirrhosis was induced in wistar rats by CCl inhalation. We generated immortalized endothelial cells from the portal vein of control (CT-iPVEC) and cirrhotic rats (CH-iPVEC) by retroviral transduction of the SV40 T antigen. We assessed differential gene expression and intracellular reactive oxygen species (ROS) levels in iPVECs and in portal veins of control and cirrhotic rats. Finally, we assessed the therapeutic effectiveness of cerium oxide nanoparticles (CeONP) on reversing PVEC activation and macrophage polarization. Results- CH-iPVECs overexpressed collagen-I, endothelin-1, TIMP-1, TIMP-2, IL-6 and PlGF genes. These results were consistent with the differential expression showed by whole portal veins from cirrhotic rats. In addition, CH-iPVECs showed a significant increase in intracellular ROS and the capacity of potentiating M1 polarization in macrophages. The treatment of CH-iPVECs with CeONPs blocked intracellular ROS formation and IL-6 and TIMP-2 gene overexpression. In agreement with the in vitro results, the chronic treatment of cirrhotic rats with CeONPs also resulted in the blockade of both ROS formation and IL-6 gene overexpression in whole portal veins. Conclusions- Endothelial cells from portal vein of cirrhotic rats depicted an abnormal phenotype characterized by a differential gene expression and the induction of M1 polarization in macrophages. We identified the excess of intracellular reactive oxygen species (ROS) as a major contributor to this altered phenotype. In addition, we demonstrated the utility of the nanomaterial cerium oxide as an effective antioxidant capable of reverse some of these pathological features associated with the portal vein in the cirrhosis condition. |
| Ajuts: | Ministerio de Economía y Competitividad SAF2015-64126-R Ministerio de Economía y Competitividad PI15-00077 Ministerio de Economía y Competitividad SAF2016-75358-R Ministerio de Economía y Competitividad MAT2015-70725-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-143 Agència de Gestió d'Ajuts Universitaris i de Recerca 2016/BP-00301 European Commission 229673 |
| Nota: | Altres ajuts: Fundació La Marató de TV3 (Marató 120930) |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Publicat a: | PloS one, Vol. 14, Num. 6 (June 2019) , art. e0218716, ISSN 1932-6203 |
