LDL impair migration of human coronary vascular smooth muscle cells and induce changes in the proteomic profile of myosin light chain

2007, Cardiovasc Res. 2007 Oct 31; [Epub ahead of print].
Padró T, Peña E, García-Arguinzonis M, Llorente-Cortes V, Badimon L.
Related authors of the center Badimon Lina, Garcia Maisa, Llorente Vicenta, Padró Teresa, Peña Esther.

AIM: High risk atheromatous plaques contain significant extra- and intracellular lipid deposits and very low smooth muscle cell numbers in the intima. However, the mechanisms inducing vessel wall remodelling and high risk plaque composition are unknown. LDL infiltrate the vessel wall and become retained and aggregated (agLDL) in the intima by binding to extracellular matrix proteoglycans. The cellular responses triggered by agLDL are not fully understood. This study was designed to investigate the effects of agLDL on vascular remodeling and repair, specifically studying human coronary vascular smooth muscle cell (VSMC) functions. METHODS AND RESULTS: Using a wound repair VSMC model system, we have shown that agLDL significantly impair cell migration. Proteomic analysis revealed a differential phenotypic pattern of myosin light chain and lower levels of phosphorylated myosin regulatory light chain (MRLC) in agLDL-exposed VSMC. LDL also induced changes in the subcellular localization of phosphorylated MRLC, with dephosphorylation strongly evident on the front edge of agLDL-treated migrating cells. PMA, a strong inducer of MLC phosphorylation, significantly reduced the effects of agLDL in VSMC migration. Inhibition of MLC kinase with ML9 did not affect MRLC dephosphorylation already induced by agLDL. CONCLUSIONS: Our results indicate that LDL impair human VSMC migration and wound repair after injury. agLDL, and to a lesser extent nLDL, induce dephosphorylation of MRLC and striking changes in the subcellular localization of phosphorylated MRLC, a cytoskeleton protein involved in VSMC migration kinetics.

Publication search

Year 198219831984198519861987198819891990199119921993199419951996199719981999200020012002200320042005200620072008200920102011 Author Aguilar ElisabethAledo RosaBadimon LinaBaldellou MaribelBayés de Luna AntoniBlanco JerónimoBorrell MariaCal RoiCalvayrac OlivierCamino SandraCasaní LauraCastellano JoséCatalina PabloCrespo JavierCubedo JuditGarcia MaisaGuadall AnnaHernández RodrigoHove-Madsen LeifJuan OriolLlorente VicentaLugano RobertaMartínez-González JoseNadal NuriaOñate BlancaPadró TeresaPeña EstherRodríguez CristinaRodriguez RicardoRomero CarolinaRubio NuriaSegalés EstefaniaSlevin MarkVilahur Gemma Search