178 - Discoidin domain-containing receptor 2 is present in human atherosclerotic plaques and involved in the expression and activity of MMP-2 (ID 828)
Abstract
Background and Aims
As a collagen receptor, Discoidin domain-containing receptor 2 (DDR2) regulates various functions of cells by activating fibrous collagens. DDR2 has been reported to be involved in atherosclerotic progression, but its pathological role remains unknown.
Methods
Using immunochemical staining, we located and compared the expression of DDR2 in the atherosclerotic plaques of humans and various animal models. To study the mechanism underlying this phenomenon, we used ox-LDL to stimulate vascular smooth muscle cells (VSMCs). Then, siRNA was applied to knockdown the DDR2 expression in VSMCs, and the migration, proliferation and collagen I-induced expression of matrix metalloproteinases (MMPs) were evaluated.
Results
In the current study, we found that an abundance of DDR2 was present in the atherosclerotic plaques of humans and various animal models and was distributed around fatty and necrotic cores, indicating that this receptor might be involved in plaque stabilization. After incubation of ox-LDL, DDR2 was upregulated in VSMCs in response to such a pro-atherosclerotic condition. Next, we found that decreased DDR2 expression in VSMCs inhibited the migration, proliferation and collagen I-induced expression of matrix metalloproteinases (MMPs). Moreover, we found that DDR2 strongly associated with the protein expression and activity of MMP-2, suggesting that DDR2 might play a role in the etiology of unstable plaques.
Conclusions
Considering that DDR2 is present in the atherosclerotic plaques of humans and various animal models and is associated with collagen I-induced secretion of MMP-2 in VSMCs, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.
