| Background Percutaneous Transluminal Coronary Angioplasty(PTCA) and stent implantation are becoming popular treatment for coronary heart disease. However, there still has 10%~30% post-operative restenosis rate, which attenuates their long-term treatment effect a lot. Etiological mechanisms remain unknown. It seems related with thrombosis, intimal hyperlasia, ECM deposition, elastic recoil, apoptosis, oxidative stress and unfavorate arterial reconstruction. Clinic research and experimental study show that excessive healing after the injury is the key problem. A few cytokines secrete abnormally, which facilitate smooth muscle cells proliferation, migration and ECM secretion. ECM is the main component of neointimae, it is also the main component that take part in arterial reconstruction. MMPs , important matrix degradation enzymes, play a key role in the degradation of ECM. In the balloon injury model of raU rabbit and pig, the expression of MMP-2 and MMP-9 enhanced in earlier phase, which suggest they may play a key part in migrationof smooth muscle cells^ formation of neointimae and reconstruction of arterial vessels. Experimental study and clinic research demonstrate that neointimae area in stent implantation is about twice as that in balloon angioplasty, and compared with balloon angioplasty , stent implantation results in more severe and long lasting MMP-2 activity and MMP-9 expression. It seems MMPs, especially MMP-2, MMP-9, contribute to migration of VSMCs and degration of ECM after artery injury.Magnetic field has a broad biological effect, which may influence transcription and translation of cultrured cell gene and alter cell trans-membrane signal transduction, facilitate endothelial cells function, inhibite VSMCs proliferation. In injury lesion, it can promote tissue healing. Most enzymes, under the influence of magnetic field, have the tendency of enhanced activity. Thus, we developed a new type intra-coronary stent梞agnetic stent. Experimental research and I phase clinic study have shown a better result compared with non-magnetic stent, in-stent restenosis and other clinic event decreased significantly. However, the mechanism is unclear. We hypothesize that the mechanism for magnetic stent to prevent in-stent restenosis may relate with lower MMPs activity and/or modulation of MMP/TIMP ratio. The objective of the study is to explore the change of MMPs after magnetic and non-magnetic stent implantation, to offer the experimental basis for the clinic use of magnetic stent.Methods Using transmission electron microscope, to investigate the preventive effect of magnetic stent on coronary restenosis after PTCA by observing the ultra-microstructure change of iliac artery aftercommon and magnetic stent in rabbits.The changes of MMPs and TIMPs were studied at various time points in the injured arteries by use of morphometric analysis, zymography, western blot and RT-PCR. Results and Conclusions1. 12 weeks after operation, morphology analysis showed that VSMC proliferation in neointimae of iliac artery in MS group was much lower than that of NMS group, p<0. 01. 7 days after the operation, there were more myofibroblasts migrated from adventitia to tunica media and intima in common stent group than magnetic stent group. Inside the media and intimae, there were many synthetic type VSMCs, ECM composed mainly collegen and elastin. At the time of 30 days after operation, most VSMCs under the intima of magnetic group had transformed to contractile type, and ECM composed mainly collegen and elastin. But VSMCs under the intima in non-magnetic group were still synthetic type, around the VSMCs, there was a lot of ECM, which mainly composed of proteoglycans and glycoproteins.2. SDS-PAGE Zymography demonstrated that proMMP-2 and MMP-2 activity in NMS group was much higher than that of BA and MS group at time of one and four weeks, p<0. 05, and the peak point in each group all appeared at four weeks after operation. At 12 weeks after operation, proMMP-2 in NMS and MS group were a little b...
|
PDF Full Text Request