Discoidin Domain-Containing Receptor 2 Is Present in Human Atherosclerotic Plaques and Involved in the Expression and Activity of MMP-2.

Abstract

Discoidin domain-containing receptor 2 (DDR2) has been suggested to be involved in atherosclerotic progression, but its pathological role remains unknown. Using immunochemical staining, we located and compared the expression of DDR2 in the atherosclerotic plaques of humans and various animal models. Then, siRNA was applied to knock down the expression of DDR2 in vascular smooth muscle cells (VSMCs), and the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs) were evaluated. 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. After incubation of oxidized low-density lipoprotein (ox-LDL), DDR2 was upregulated in VSMCs in response to such a proatherosclerotic condition. Next, we found that decreased DDR2 expression in VSMCs inhibited the migration, proliferation, and collagen Ι-induced expression of matrix metalloproteinases (MMPs). Moreover, we found that DDR2 is strongly associated with the protein expression and activity of MMP-2, suggesting that DDR2 might play a role in the etiology of unstable plaques. Considering that DDR2 is present in the atherosclerotic plaques of humans and is associated with collagen Ι-induced secretion of MMP-2, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.

• Authors: Qi Yu, Ruihan Liu, Ying Chen, Ahmed Bilal Waqar, Fuqiang Liu, Juan Yang, Ting Lian, Guangwei Zhang, Hua Guan, Yuanyuan Cui, Cangbao Xu
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 1010496 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34956435 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Qi Yu et al.

Chemical References

• RNA, Small Interfering
• Discoidin Domain Receptor 2
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Animals
• Cell Movement
• Cell Proliferation
• Discoidin Domain Receptor 2 (genetics)
• Disease Models, Animal
• Humans
• Matrix Metalloproteinase 2 (metabolism)
• Mice
• Plaque, Atherosclerotic (genetics, pathology)
• RNA, Small Interfering (metabolism)
• Rabbits