Low-density lipoproteins impair migration of human coronary vascular smooth muscle cells and induce changes in the proteomic profile of myosin light chain.
OBJECTIVE
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. Low-density lipoproteins (LDLs) 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 remodelling and repair, specifically studying human coronary vascular smooth muscle cell (VSMC) functions.


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 (P-MRLC) in agLDL-exposed VSMC. LDL also induced changes in the subcellular localization of P-MRLC, with dephosphorylation strongly evident on the front edge of agLDL-treated migrating cells. PMA, a strong inducer of myosin light chain (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 LDLs 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 P-MRLC, a cytoskeleton protein involved in VSMC migration kinetics.
Padró
Teresa
T
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Av. S. Antoni M. Claret,167, 08025 Barcelona, Spain.
Peña
Esther
E
García-Arguinzonis
Maisa
M
Llorente-Cortes
Vicenta
V
Badimon
Lina
L
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000032:analysis; D006801:Humans; D008077:Lipoproteins, LDL / Q000633:toxicity*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D018994:Myosin Light Chains / Q000032:analysis*; D009219:Myosin-Light-Chain Kinase / Q000502:physiology; D043263:Myosin-Light-Chain Phosphatase / Q000502:physiology; D010766:Phosphorylation; D040901:Proteomics; D014945:Wound Healing
D003598:Cytoskeletal Proteins; D008077:Lipoproteins, LDL; D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase