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Expression changes and roles of matrix metalloproteinases in a rat model of traumatic deep vein thrombosis
Yu-bing Zhang1, Wen Li, Li-qing Yao
1Department of Orthopaedics, First Affiliated Hospital of Kunming Medical College, China.
Objective:
To study the expression changes of matrix metalloproteinases (MMPs) in traumatic deep vein thrombosis (TDVT) in a rat model with the aid of gene chip technology and to explore the roles of MMPs in TDVT.
Methods:
Totally 150 Sprague Dawley rats were randomly divided into control group (n equal to 10) and model group (n equal to 140). Rat models of TDVT were established by clamping the femoral vein and fixing the bilateral hind limbs. Then fixation of the hip spica with plaster bandage was conducted. According to the observation phases and/or biological situations of the femoral vein thrombosis, the model rats were further divided into 7 groups. Vascular tissues were obtained from each group through noninvasive incision into the femoral vein at corresponding time points. We adopted the Trizol one-step method for total RNA extraction, Affymetrix RAT 230 2.0 array for detection of RNA expressions and fold change (FC) analysis for changes of differential expressions of MMPs in each group. The main outcome parameters measured included expressions of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13, MMP-14, MMP-16, MMP-23 and MMP-24. Gene array data of these MMPs were analyzed by the Affymetrix Microarray Analysis software (Version 5.0).
Results:
FC analysis showed differential expressions of MMPs in each group during the course of TDVT. At the initial period of thrombosis, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, and MMP-24 had significantly high expression, while MMP-12, MMP-13, MMP-14, MMP-16 and MMP-23 had relatively low expression. MMPs were all highly expressed at the peak time of thrombosis. In the process of thrombus resolution, MMP-2, MMP-10, MMP-16 and MMP-24 have relatively low expression, while MMP-12, MMP-13, MMP-14, MMP-16 and MMP-23 have significantly high expression.
Conclusion:
MMPs may affect the process of TDVT through transcription regulation of the fibrinolysis-anti-fibrinolytic system during the course of thrombosis and thrombus resolution.
Insights
Matrix metalloproteinases (MMPs) show dynamic expression changes during traumatic deep vein thrombosis (TDVT) in rats. These MMPs influence thrombosis and resolution by regulating the fibrinolysis-anti-fibrinolytic system.
Area of Science:
- Biochemistry
- Molecular Biology
- Vascular Biology
Background:
- Traumatic deep vein thrombosis (TDVT) is a significant clinical concern.
- Matrix metalloproteinases (MMPs) are implicated in various physiological and pathological processes, including tissue remodeling and inflammation.
- Understanding the role of MMPs in TDVT is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the differential expression profiles of various matrix metalloproteinases (MMPs) during the development and resolution of traumatic deep vein thrombosis (TDVT) in a rat model.
- To explore the potential roles of these MMPs in the pathogenesis and resolution of TDVT.
Main Methods:
- A rat model of traumatic deep vein thrombosis (TDVT) was established.
- Gene chip technology (Affymetrix RAT 230 2.0 array) was employed for high-throughput analysis of RNA expression.
- Differential gene expression of MMPs was analyzed using fold change (FC) analysis at various time points during thrombosis and resolution.
Main Results:
- Significant differential expression of multiple MMPs was observed throughout the course of TDVT.
- At the initial stage of thrombosis, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, and MMP-24 showed high expression, while MMP-12, MMP-13, MMP-14, MMP-16, and MMP-23 were lowly expressed.
- During thrombus resolution, a shift in MMP expression occurred, with MMP-2, MMP-10, MMP-16, and MMP-24 showing lower expression and MMP-12, MMP-13, MMP-14, MMP-16, and MMP-23 exhibiting significantly higher expression.
Conclusions:
- Matrix metalloproteinases (MMPs) play a dynamic role in traumatic deep vein thrombosis (TDVT).
- MMP expression patterns change significantly during thrombosis and thrombus resolution.
- These MMPs likely influence TDVT progression and resolution through the regulation of the fibrinolysis-anti-fibrinolytic system.
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