Author, as appears in the article.: Girona J; Rosales R; Plana N; Saavedra P; Masana L; Vallvé J
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Girona Tell, Josefa / Masana Marín, Luis / Plana Gil, Núria / ROSALES RIBAS, ROSER / SAAVEDRA GARCIA, PAULA / Vallvé Torrente, Joan Carles
Abstract: Purpose: The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and Results: A DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 μM) and PD98059 (10 μM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. Conclusions: These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs. © 2013 Girona et al.
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licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 19326203
Author's mail: josefa.girona@urv.cat jc.vallve@urv.cat josefa.girona@urv.cat jc.vallve@urv.cat luis.masana@urv.cat
Author identifier: 0000-0002-6267-8779 0000-0002-6267-8779 0000-0002-0789-4954
Record's date: 2024-11-16
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081914
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Plos One. 8 (11): e81914-e81914
APA: Girona J; Rosales R; Plana N; Saavedra P; Masana L; Vallvé J (2013). FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway. Plos One, 8(11), e81914-e81914. DOI: 10.1371/journal.pone.0081914
Article's DOI: 10.1371/journal.pone.0081914
Entity: Universitat Rovira i Virgili
Journal publication year: 2013
Publication Type: Journal Publications
Repositori URV