Document Detail


Aggregated low density lipoprotein induce impairment of the cytoskeleton dynamics through UPA/UPAR in human VSMC.
MedLine Citation:
PMID:  22906080     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Urokinase-type plasminogen activator (UPA) regulates vascular smooth muscle cell (VSMC) functions relevant in vascular remodeling by facilitating proteolysis at the cell surface and inducing cell signaling pathways. Our previous results demonstrated that aggregated low density lipoprotein (agLDL) impair cytoskeleton dynamics, a key event contributing to VSMC behavior during progression of atherosclerotic plaques. Objectives: To investigate whether mechanisms underlying inhibition of cytoskeleton dynamics in lipid-loaded VSMC occurs through a UPA mediated process. Methods: Adhesion assay was performed in lipid-loaded human VSMC after 16 hours exposition to agLDL (100 μg/mL). Protein subcellular localization and actin-fiber formation were assessed by confocal microscopy. For analysis of protein expression western blots were carried out. Co-immunoprecipitates of UPAR were examined by 1D- or 2D-electrophoresis, mass-spectrometry MALDI-TOF and western blot. Results: agLDL induced UPA subcellular delocalization and significantly decreased UPA levels during attachment of VSMC. UPA (enhanced endogenous-expression or exogenous added) acting as UPAR-ligand restored actin-cytoskeleton-organization and adhesion capacity of lipid-loaded cells to control levels. UPAR co-immunoprecipitated with the unphosphorylated form of myosin regulatory light chain (MRLC) in lipid-loaded cells. The detrimental effects of agLDL on MRLC phosphorylation were reversed by high levels of UPA. The UPA effects on VSMC exposed to agLDL involved FAK phosphorylation. Conclusions: The detrimental effects of atherogenic LDL on VSMC are mediated by a decrease and delocalization of UPA-UPAR interaction that result in an impairment of cytoskeleton dynamics and adhesion capacity affecting cell-phenotype and function. © 2012 International Society on Thrombosis and Haemostasis.
Authors:
R Lugano; E Peña; L Badimon; T Padró
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-20
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Affiliation:
Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant- Pau (IIB-Sant Pau), Barcelona. Spain CiberOBN, Institute Carlos III, Barcelona. Spain Autonomous University of Barcelona, Barcelona. Spain.
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