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Título: | Distinct Regulation of Mitogen-activated Protein Kinases and p27Kip1 in Smooth Muscle Cells from Different Vascular Beds: A potential role in establishing regional phenotypic variance |
Autor: | Castro, Claudia; Díez-Juan, Antonio CSIC ORCID; Cortés, María José CSIC; Andrés, Vicente CSIC ORCID | Fecha de publicación: | feb-2003 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Journal of Biological Chemistry 278(7): 4482-4490 (2003) | Resumen: | Excessive proliferation and migration of vascular smooth muscle cells (SMCs) participate in atherosclerotic plaque growth. In this study, we investigated whether SMCs from vessels with different atherogenicity exhibit distinct growth and migratory potential and investigated the underlying mechanisms. In fat-fed rabbits, we found increased cell proliferation and atheroma formation in the aortic arch versus the femoral artery. When examined in culture, SMCs isolated from the aortic arch (ASMCs) displayed a greater capacity for inducible proliferation and migration than paired cultures of femoral artery SMCs. Two lines of evidence suggested that distinct regulation of the growth suppressor p27Kip1(p27) contributes to establishing these phenotypic dissimilarities. First, p27 expression was comparably lower in ASMCs, which exhibited a higher fraction of p27 phosphorylated on Thr-187 and ubiquitinated. Second, forced p27 overexpression in ASMCs impaired their proliferative and migratory potential. We found that platelet-derived growth factor-BB-dependent induction of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway was comparably higher in ASMCs. Importantly, pharmacological inhibition of MAPKs increased p27 expression and attenuated ASMC proliferation and migration. In contrast, forced MAPK activation diminished p27 expression and markedly augmented femoral artery SMC proliferation and migration. We propose that intrinsic differences in the regulation of MAPKs and p27 play an important role in creating variance in the proliferative and migratory capacity of vascular SMCs, which might in turn contribute to establishing regional variability in atherogenicity. | Descripción: | 9 páginas, 9 figuras.-- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.-- El documento en word es la versión post-print. | Versión del editor: | http://www.jbc.org/content/278/7/4482.abstract | URI: | http://hdl.handle.net/10261/36852 | ISSN: | 0021-9258 |
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J. Biol. Chem. 278 4482-4490 (2003).doc | 2,53 MB | Microsoft Word | Visualizar/Abrir |
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