title: Aggregated low density lipoproteins decrease metalloproteinase-9 expression and activity in human coronary smooth muscle cells.
abstract: Plaque stability largely depends on vascular smooth muscle cell (VSMC) function. VSMC secrete metalloproteinases (MMPs), matrix degrading endopeptidases, that regulate VSMC migration and function. Among them, gelatinase B or MMP-9 seems to have a protective effect by promoting a stable plaque phenotype. In macrophage foam cells oxidized LDL (oxLDL) uptake regulates MMP-9 expression. However, it is unknown whether VSMC-lipid loading by aggregated LDL (agLDL) internalization produces any effect on MMP-9 production by human resident vascular cells. In the present study, we analyzed the effect of lipid-internalization in MMP-9 and MMP-2 expression and activity and its consequences in VSMC migration. Our results show that agLDL-internalization down-regulates MMP-9 activity in a time-dependent manner up to 42% at 48h and in a dose-dependent manner up to 87% at 300 microg/mL. nLDL induced similar but not sustained decrease on MMP-9 activity. However, neither agLDL nor nLDL exerted any significant effect on MMP-2 and TIMP-1. VSMC regrowth after a scratch injury was significantly reduced by exposure to agLDL. We conclude that agLDL-lipid loading reduces MMP-9 activity and this effect is associated to inhibition of VSMC migration. Thus, agLDL internalization may have consequences on vascular remodeling after injury, and the stability of lipid-rich atherosclerotic plaques.
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC-HSCSP, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Otero-Viñas
authors.forename: Vicenta
authors.initials: V
authors.lastname: Llorente-Cortés
authors.forename: Ester
authors.initials: E
authors.lastname: Peña
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D015536:Down-Regulation; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D008077:Lipoproteins, LDL; D020780:Matrix Metalloproteinase 9