TDVT is one of common complications of clinical orthopedics. It is reported that the incidence of DVT is about 56-160/10 000 000 people each year in America[6], the elderly close to 1%[7]. DVT patients are about 10 000 000 each year in China[8]. The incidence of pulmonary embolism after coronary heart disease and high blood pressure, is the third largest cause of death[8-9]. Some data confirm that only 11%-15% of patients are diagnosed before death as pulmonary embolism[10-11]. Therefore, the study of TDVT mechanism is of great value. Studies have shown that MMPs participates in TDVT[12]. In this experimental study, we found that the expression of MMPs exhibited differential expressions in different time points, indicating the expression of MMPs participates in regulating thrombosis and resolution.
MMPs are a family by the Zn2+ dependent endopeptidase family of enzymes, it is the major media of extracellular matrix involving in degradation and remodeling, participating in many physiological and pathological processes in human body[13-14], widely expressed in vivo[15]. In 1962, Gross and Lapiere found the MMP (namely MMP-1). The MMPs have been found so far nearly 30 species, and 26 kinds of MMPs have been identified and sequenced[16]. MMPs are divided into five subtypes: collagenase, enzymes matrilysin, gelatinases, membrane proteases and other subtypes, the first three MMPs are located in the cytoplasm, membrane proteases express in the cell membrane[17]. Aa a non-active form of secretion, MMPs can be activated by protein hydrolysis, also be inhibited by some special TIMPs and ethylene diamine tetraacetic acid[18-19]. Through the positive feedback role, the activated MMPs could promote the activation of plasminogen and induce cascade reaction[20].
MMPs which is extracellular activation can degrade all the extracellular matrix components out of polysaccharide involving in growth, development and tissue repair and other physiological processes[21]. The activity of matrix degradation is a marked increasing after the expression of MMPs increased[22]. Study shows that MMP-9 and MMP-2 involve in regulation of vascular wall damage modeling and early repair of the transfer of collagen and matrix[23]. Visse et al[24] confirmed that MMP-2 and MMP-9 are closely related into the activities of angiogenesis and proteins, which come from collagen fibers in the thrombolytic process, and their reasons may be due to the u-PA activation of the MMP-2 and MMP-9. In this experiment, the expression of MMPs by gene chip test in the formation of the early and the peak time was significant hightened, indicating their participation in the thrombus formation process, and may serve as a catalyst. In the thrombus resulotion process, the expression of MMPs slightly rose up, in line with foreign research reports[25-27].
TIMPs family are coding proteins secreted by a cell which also secreted metalloproteinases, and they have the synthetic multi-gene family encoding proteins with MMPs and their activation of the zymogen form of combination[28]. TIMPs are the major physiological inhibitor of MMPs, and have already identified four kinds, with a specific inhibition of MMPs[29]. Under normal circumstances, the tissues keeps a balance between MMPs and TIMPs. Their interaction is the decision of extracellular matrix degradation or aggregation[30]. In this experiment, the expression of TIMPs by gene chip test in the formation of the early and the peak time was different, indicating their participation in the thrombus formation process, and may serve as a catalyst. In the thrombus sulotion process, the expression of TIMPs slightly rose up, in which the expression of TIMP1 was mild high. TIMP 2 and 3 were significantly lower expression on their participation in the process of thrombosis. TIMPs may play a major inhibitory role in TDVT.
In summary, this experiment revealed that MMPs may play an important role in TDVT. MMPs were activated during the course of thrombosis, then through the positive feedback role in promoting the activation of plasminogen and occurring the activation cascade. In the course of thrombus insolution, MMPs continued to show a high expression, indicating in which they may have played a positive role in repair. The expression of TIMPs was significantly inhibited both in the thrombus formation and resolution process. Therefore, the imbalance of MMPs/TIMPs can be one of the most important factors to influence the biological states of TDVT, and its mechanism would be further studied.
