Author, as appears in the article.: Serra N; Rosales R; Masana L; Vallvé J
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Masana Marín, Luis / ROSALES RIBAS, ROSER / Serra Encinas, Noemi / Vallvé Torrente, Joan Carles
Keywords: Statin therapy Stabilization Protein fibulin-1 Plaque neovascularization Mechanisms Matrix Disease Collagen content Binding Atherosclerotic plaques
Abstract: © 2015 Serra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The composition and structure of the extracellular matrix (ECM) in the vascular wall and in the atherosclerotic plaque are important factors that determine plaque stability. Statins can stabilize atherosclerotic plaques by modulating ECM protein expression. Fibulins are important components of the ECM. We evaluated the in vitro effect of simvastatin on the expression of fibulin-1, -2, -4 and -5 in human coronary artery smooth muscle cells (SMCs) and the mechanisms involved. Cells were incubated with simvastatin (0.05-1 μM), mevalonate (100 and 200 μM), geranylgeranyl pyrophosphate (GGPP) (15 μM), farnesyl pyrophosphate (FPP) (15 μM), the Rho kinase (ROCK) inhibitor Y-27632 (15 and 20 μM), the Rac-1 inhibitor (another member of Rho family) NSC23766 (100 μM), arachidonic acid (a RhoA/ROCK activator, 25-100 μM) and other fatty acids that are not activators of RhoA/ROCK (25- 100 μM). Gene expression was analyzed by quantitative real-time PCR, and fibulin protein levels were analyzed by western blotting and ELISA. Simvastatin induced a significant increase in mRNA and protein levels of fibulin-2 at 24 hours of incubation (p<0.05), but it did not affect fibulin-1, -4, and -5 expression. Mevalonate and GGPP were able to reverse simvastatin's effect, while FPP did not. In addition, Y-27632, but not NSC23766, significantly increased fibulin-2 expression. Furthermore, activation of the RhoA/ROCK pathway with arachidonic acid decreased fibulin-2 mRNA. Simvastatin increased mRNA levels and protein expression of the ECM protein fibulin-2 through a RhoA and Rho-Kinase-mediated pathway. This increase could affect the composition and structure of the ECM.
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licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 19326203
Author's mail: jc.vallve@urv.cat noemi.serra@urv.cat jc.vallve@urv.cat luis.masana@urv.cat
Author identifier: 0000-0002-2277-351X 0000-0002-0789-4954
Record's date: 2024-10-26
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133875
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Plos One. 10 (7): e0133875-
APA: Serra N; Rosales R; Masana L; Vallvé J (2015). Simvastatin increases fibulin-2 expression in human coronary artery smooth muscle cells via RhoA/Rho-Kinase signaling pathway inhibition. Plos One, 10(7), e0133875-. DOI: 10.1371/journal.pone.0133875
Article's DOI: 10.1371/journal.pone.0133875
Entity: Universitat Rovira i Virgili
Journal publication year: 2015
Publication Type: Journal Publications
Repositori URV