Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression

Atherosclerosis. 2009 Feb;202(2):415-23. doi: 10.1016/j.atherosclerosis.2008.04.050. Epub 2008 May 22.


Background and aims: Atherosclerosis is a chronic inflammatory process involving the activity of several cytokines and growth factors. Platelet-derived growth factor-A (PDGF-A) and PDGF-B are important mitogens and chemoattractants for monocytes as well as smooth muscle cells. We sought to identify the role of PDGF-C and PDGF-D, two new members of the PDGF family, in monocyte migration and differentiation. We also assessed their effects in regulating matrix metalloproteinase-2 (MMP-2) and MMP-9, which are important for cell migration.

Methods and results: PDGF-C and PDGF-D were expressed in macrophages, smooth muscle cells, and endothelial cells in human atherosclerotic plaques, as shown by immunohistochemical analysis. PDGF-C and PDGF-D mRNA and protein expression was induced after differentiation of THP-1 monocytes to macrophages, and both PDGF-C and PDGF-D induced MMP-9 mRNA expression in a concentration-dependent manner. Treatment of cells with PDGF-C or PDGF-D enhanced the secretion of MMP-2 and MMP-9 in a cell-dependent manner. In a migration assay using a Boyden chamber with 8 microm pore size, PDGF-C and PDGF-D attracted THP-1 monocytes in a concentration-dependent manner.

Conclusions: Our data suggest that PDGF-C and PDGF-D, like PDGF-A and PDGF-B, play important roles in atherosclerosis by stimulating MMP activity and influencing monocyte migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autocrine Communication / physiology
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / metabolism
  • Carotid Artery Diseases / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / immunology*
  • Cytokines / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / immunology
  • Humans
  • Leukemia
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Lymphokines / pharmacology
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 9 / genetics*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism*
  • Platelet-Derived Growth Factor / pharmacology
  • RNA, Messenger / metabolism


  • Cytokines
  • Lymphokines
  • PDGFD protein, human
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • platelet-derived growth factor C
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9