| Percutaneous transluminal coronary angioplasty (PTCA), an important method for treatment ischemic heart diseases, has been used extensively. But the high incidence of restenosis after PTCA is the vital limitation for its long term effect. Although the exact mechanism in restenosis is still not very clear, it is believed to be related to many events such as vascular smooth muscle cell (VSMC) proliferation and migration, excessive synthesis of extracellular matrix (ECM) as well as ECM remodeling and so on. Increasing studies have demonstrated that focal adhesion kinase (FAK), a non-receptor tyrosine kinase, involves in the intracellular signal transduction mediated by integrin. Phosphorylation of FAK itself and following proteins is the key link in the interactions between ECM and cells which in rum show a series of biological effects, including cell proliferation, migration and apoptosis. But up to date whether or not FAK as an important signal molecule plays a role in pathogenesis of restenosis after endothelium injury still remain uncertain.There are no satisfactory methods and medicines to treat restenosis so far because of the complicated mechanisms in the development of restenosis. Many studies showed that the functional features of Chinese Traditional Medicine (TCM) reflect its superiority in preventing and treating vascular restenosis. According to the theories of TCM, restenosis is a kind of "blood stasis", and supplementing Qi, activating blood circulation to eliminate stasis should be used as therapeutic principles. Our previous experiments have showed that the recipe of supplementing Qi, activating blood circulation to eliminate stasis, including Astragalus Membranaceus(Ast) and Angelica Sinensis (Ang), could effectively prevent intimal hyperplasia by adjusting the balances of tPA/PAI and TXA2/PGI2, inhibiting proliferation of VSMC and excessive formation of ECM. On the basis of our previous studies, we used Ast and Ang, as two therapeutic medicines, and investigated their effects on FAK expression and activation. So, we could further explore the mechanisms in intimal hyperplasia caused by de-endothelialization and provide theoretical basis for finding new therapeutic targets in arresting restenosis by TCM.1. FAK expression and activation in the development of restenosis after vascular de-endothelializationThe restenosis model was established by denuding the rat aorta endothelium with balloon catheter. The pathological features of arterial wall, changes of hemodynamics, NO content in plasma as well as activities of FAK expression and phosphorylation were observed. The results are as follows:1.1 Compared with smooth intima and orderly arranged medial VSMC of aorta in the normal rats, rough intima was first seen on day 3 after de-endothelialization, and on day 7, focal VSMC proliferation in neointima and disordered medial VSMC nuclei were found in injured area. On day 14 to 21, progressive and widespread intimal thickening and lumen stenosis were observed.Image analysis showed that both thickness ratio and area ratio of intima/media (I/M) increased, and the diameter of lumen decreased on day 7 after de-endothelialization. On day 21, the two ratios reached 1.97 and 1.13, respectively. It implied that restenosis was successfully elicited by endothelial denudation.1.2 The maximal and minimal blood velocity began to decrease on day 3 after endothelial denudation and got to the lowest point on day 21. In contrast, pulsatile index (PI) and resistance index (RI) increased from day 3 after de-endothelialization, and the highest values were obtained on day 21 and 14, respectively.1.3 Compared with low level expression and low-phosphorylation of FAK in aorta of control rat, amount of FAK mRNA and protein as well as degree of FAK phosphorylation increased by 36.4%, 35% and 60%, respectively, on day 3 after de-endothelialization. On day 7 the amount of FAK mRNA and protein reached the peak, and began to decrease on day 14. On day 21, the activity of FAK gene expression and level of p...
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