Low-Density Lipoproteins Induce Heat Shock Protein 27 Dephosphorylation, Oligomerization, and Subcellular Relocalization in Human Vascular Smooth Muscle Cells
Por:
Garcia-Arguinzonis, M, Padro, T, Lugano, R, Llorente-Cortes, V, Badimon, L
Publicada:
1 jun 2010
Resumen:
Objective-High levels of circulating low-density lipoproteins (LDL) are a major atherosclerotic risk factor. The effects of intimal LDL on vascular smooth muscle cell (VSMC) phenotype and function during plaque remodeling and vascular repair are not fully understood. We have investigated whether exposure of VSMC to LDL induces changes on the proteomic profile of the heat shock protein (HSP) family-molecular chaperones involved in atherosclerosis.
Methods & Results-2D electrophoresis demonstrates that LDL modifies the proteomic profile of HSP27 (HSPB1). Western blot analysis evidenced a significant HSP27 dephosphorylation after exposure of cells to native LDL (nLDL) and aggregated-LDL (agLDL) for 24 hours (P<0.05). Dephosphorylation of HSP27 was not related to changes in p38(MAPK) phosphorylation. Both nLDL and agLDL induced relocalization of unphosphorylated HSP27 to the tip of actin stress fibers and focal adhesion structures in VSMC. During cell adhesion, phospho-HSP27 was located at the cell surface contact region in LDL-treated cells, whereas it remained cytosolic in control cells. Immunohistochemistry studies showed that phosphorylated HSP27 is rarely found in lipid-rich areas of atherosclerotic plaques in human coronary arteries.
Conclusion-Our results indicate that in VSMC, LDL modulate HSP27 phosphorylation and subcellular localization, affecting actin polymerization and cytoskeleton dynamics. (Arterioscler Thromb Vasc Biol. 2010; 30: 1212-1219.)
Filiaciones:
Garcia-Arguinzonis, M:
Hosp Santa Creu & St Pau UAB, CSIC, Cardiovasc Res Ctr, Barcelona, Spain
Hosp Santa Creu & St Pau UAB, ICCC, Barcelona, Spain
Inst Carlos III, Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Padro, T:
Hosp Santa Creu & St Pau UAB, CSIC, Cardiovasc Res Ctr, Barcelona, Spain
Hosp Santa Creu & St Pau UAB, ICCC, Barcelona, Spain
Lugano, R:
Hosp Santa Creu & St Pau UAB, CSIC, Cardiovasc Res Ctr, Barcelona, Spain
Hosp Santa Creu & St Pau UAB, ICCC, Barcelona, Spain
Inst Carlos III, Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
Llorente-Cortes, V:
Hosp Santa Creu & St Pau UAB, CSIC, Cardiovasc Res Ctr, Barcelona, Spain
Hosp Santa Creu & St Pau UAB, ICCC, Barcelona, Spain
Badimon, L:
Hosp Santa Creu & St Pau UAB, CSIC, Cardiovasc Res Ctr, Barcelona, Spain
Hosp Santa Creu & St Pau UAB, ICCC, Barcelona, Spain
Inst Carlos III, Inst Salud Carlos III, Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Barcelona, Spain
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