Lactosylceramide promotes cell migration and proliferation through activation of ERK1/2 in human aortic smooth muscle cells

Am J Physiol Heart Circ Physiol. 2009 Jul;297(1):H400-8. doi: 10.1152/ajpheart.01254.2008. Epub 2009 May 22.


Increased plasma levels of lactosylceramide (LacCer) have been associated with cardiovascular disease. However, it is largely unknown whether LacCer directly contributes to dysfunction of smooth muscle cells (SMCs), a key event in vascular lesion formation. In the present study, we determined the effects and potential mechanisms of LacCer on cell migration and proliferation in human aortic SMCs (AoSMCs). Cell migration and proliferation were determined by a modified Boyden chamber assay and nonradioactive colorimetric (MTS) assay, respectively. We found that LacCer significantly induced AoSMC migration and proliferation in a concentration- and time-dependent manner. In addition, LacCer significantly upregulated the expression of PDGFR-B, integrins (alpha(v) and beta(3)), and matrix metalloproteinases (matrix metalloproteinase-1 and -2) at both mRNA and protein levels, as determined by real-time PCR and Western blot analyses, respectively. Furthermore, LacCer increased superoxide anion production and the transient phosphorylation of ERK1/2 in AoSMCs, as determined by dihydroethidium staining and immunoassay, respectively. Accordingly, LacCer-induced cell migration and proliferation were effectively blocked by antioxidants (seleno-l-methionine and Mn tetrakis porphyrin) and by a specific ERK1/2 inhibitor. Thus, LacCer promotes cell migration and proliferation through oxidative stress and activation of ERK1/2 in AoSMCs. These findings demonstrate the functional role of LacCer in the vascular disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigens, CD / pharmacology*
  • Antioxidants / pharmacology
  • Atherosclerosis / pathology
  • Blotting, Western
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Enzyme Activation / drug effects
  • Flow Cytometry
  • Graft Occlusion, Vascular / pathology
  • Humans
  • Lactosylceramides / antagonists & inhibitors
  • Lactosylceramides / pharmacology*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 1 / physiology*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mitogen-Activated Protein Kinase 3 / physiology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology*
  • Oxidative Stress / drug effects
  • RNA / biosynthesis
  • RNA / genetics
  • Superoxides / metabolism
  • Wound Healing / drug effects


  • Antigens, CD
  • Antioxidants
  • Lactosylceramides
  • Superoxides
  • CDw17 antigen
  • RNA
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3