期刊
ATHEROSCLEROSIS
卷 202, 期 2, 页码 415-423出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2008.04.050
关键词
Protease; Growth factor; Extracellular matrix; Atherosclerosis
资金
- Swedish Research Council [12660]
- Swedish Heart-Lung foundation
- Nanna Svartz foundation
- Loo and Hans Ostermans Foundation
- Lars Hierta Memorial Foundation
- Anders Otto Swards Foundation/Ulrika Eklunds Foundation
- Gun and Bertil Stohnes Foundation
- Stockholm County Council
Background and nuns: 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 monocytcs 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-I) 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 mu m 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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