scholarly journals Discoidin domain-containing receptor 2 is present in human atherosclerotic plaques and involved in the expression and activity of MMP-2

2020 ◽  
Author(s):  
Yu Qi ◽  
Ruihan Liu ◽  
Ying Chen ◽  
Ahmed Bilal Waqar ◽  
Fuqiang Liu ◽  
...  

Abstract Background: DDR2 has been suggested 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. Then, siRNA was applied to knockdown the expression of DDR2 in smooth muscle cells (VSMCs), and the migration, proliferation and collagen I-induced expression of matrix metalloproteinases (MMPs) were evaluated. Results: 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 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. Conclusion: Considering that DDR2 is present in the atherosclerotic plaques of humans and is associated with collagen I-induced secretion of MMP-2, the clinical role of DDR2 in cardiovascular disease should be elucidated in further experiments.

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Qi Yu ◽  
Ruihan Liu ◽  
Ying Chen ◽  
Ahmed Bilal Waqar ◽  
Fuqiang Liu ◽  
...  

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.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mihaela G Ionita ◽  
Gerard Pasterkamp ◽  
Dominique deKleijn

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.


2015 ◽  
Vol 13 (2) ◽  
pp. 161-166 ◽  
Author(s):  
Sebastien Lenglet ◽  
Fabrizio Montecucco ◽  
Francois Mach

2015 ◽  
Vol 56 (9) ◽  
pp. 5218 ◽  
Author(s):  
Hema S. Aluri ◽  
Claire L. Kublin ◽  
Suharika Thotakura ◽  
Helene Armaos ◽  
Mahta Samizadeh ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
pp. 9-16
Author(s):  
Diana Opincariu ◽  
Nora Rat ◽  
Imre Benedek

Abstract Extracellular matrix (ECM) plays an important role in the development and progression of atherosclerotic lesions. Changes in the ECM are involved in the pathophysiology of many cardiovascular diseases, including atherosclerosis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases, also known as matrixins, with proteolytic activity in the ECM, being responsible for the process of tissue remodeling in various systemic pathologies, including cardiac and vascular diseases. MMPs play an important role in maintaining normal vascular structure, but also in secondary cardiovascular remodeling, in the formation of atherosclerotic plaques and in their vulnerabilization process. In addition to the assigned effect of MMPs in vulnerable plaques, they have a well-defined role in post-infarction ventricular remodeling and in various types of cardiomyopathies, followed by onset of congestive heart failure, with repeated hospitalizations and death. The aim of this manuscript was to provide a summary on the role of serum matrix metalloproteinases in the process of initiation, progression and complication of atherosclerotic lesions, from a molecular level to clinical applicability and risk prediction in patients with vulnerable coronary plaques.


1996 ◽  
Vol 51 (3) ◽  
pp. 216-218 ◽  
Author(s):  
Rachel G. Klein
Keyword(s):  

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