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Updated: Jul 4, 2026
Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
Published on: November 26, 2018
Effects of PDGF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression
Dick Wågsäter1, Chaoyong Zhu, Hanna M Björck
1Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Dick.Wagsater@ki.se
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.
Insights
Platelet-derived growth factors C and D (PDGF-C and PDGF-D) promote monocyte migration and matrix metalloproteinase (MMP) secretion, contributing to atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Inflammation Research
Background:
- Atherosclerosis is a chronic inflammatory disease.
- Platelet-derived growth factor-A (PDGF-A) and PDGF-B influence monocyte and smooth muscle cell behavior.
- The roles of newer PDGF family members, PDGF-C and PDGF-D, in atherosclerosis are less understood.
Purpose of the Study:
- To investigate the function of PDGF-C and PDGF-D in monocyte migration and differentiation.
- To assess the impact of PDGF-C and PDGF-D on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression and activity.
Main Methods:
- Immunohistochemical analysis of human atherosclerotic plaques.
- Quantitative analysis of PDGF-C and PDGF-D mRNA and protein expression in differentiated THP-1 monocytes.
- Cell migration assays using Boyden chambers.
- Measurement of MMP-2 and MMP-9 secretion.
Main Results:
- PDGF-C and PDGF-D were detected in macrophages, smooth muscle cells, and endothelial cells within atherosclerotic plaques.
- Differentiation of THP-1 monocytes into macrophages upregulated PDGF-C and PDGF-D expression.
- PDGF-C and PDGF-D stimulated MMP-9 mRNA expression and enhanced MMP-2 and MMP-9 secretion.
- PDGF-C and PDGF-D demonstrated chemoattractant activity for THP-1 monocytes.
Conclusions:
- PDGF-C and PDGF-D are expressed in human atherosclerotic lesions.
- These growth factors stimulate monocyte migration and MMP production, similar to PDGF-A and PDGF-B.
- PDGF-C and PDGF-D are implicated as key players in the pathogenesis of atherosclerosis.
