| Background and objectiveThe prevention and treatment of vascular restenosis after percutaneous trans- coronary angioplasty (PTCA) are a hot and difficult problem in the field of cardio- vasology. The essence of restenosis is an excess repair after vascular injury. Proliferation and migration of vascular smooth muscle cells (VSMCs) from the media to the intima as well as accumulation of extracellular matrix (ECM) are crucial pathogenic events in the progression of restenosis. The purpose of this study are to determine the effects of peroxisome proliferators-activated receptor-γ(PPAR-γ) ligand-rosiglitazone (RSG) on rat VSMCs proliferation and on neo- intimal formation in the balloon injury model of rabbit iliac artery, and to explore the involved potential molecular mechanisms. All of these will be helpful to provide a new idea for the prevention and treatment of vascular restenosis after PTCA.Methods1.The primary cultured cells were identified by morphological characteristics and immunocytochemistry withα-SMA.2. The fourth or sixth passage purified cells were harvested for the following experiments. MTT assay was used to quantitate the cell proliferating viability. RT-PCR, Western blot and immunocytochemistry were preformed to examine the mRNA and protein expressions of Akt and NF-κB respectively. ELISA was applied to analyze the concentration of TNF-α.3. The model of vascular restenosis of rabbit iliac arteries were established by balloon denudation. Serum biochemistrical index were measured.4. Sections of arteries were stained with HE and Masson and calculated in the image analyzing software.5. Immunohistochemistry was used to observe the protein expressions of PCNA,MMP-2 and TIMP-2. Results1. The cultured cells possessed"peak and valley"characteristics for VSMCs. Immunocytochemical staining with specific antibody againstα-SMA demonstrated these cells were positive.2. CXCL16 (50 ng/ml) can induce VSMCs proliferation (P<0.01), but RSG can show inhibition manner (P<0.05) .3. The mRNA and expression of Akt in the CXCL16 group increased compared to those of the control group (P<0.05), while RSG can decrease these expressions (P<0.01). The mRNA and expression of NF-κB had similar tendency with those of Akt.4. The level of TNF-αof the CXCL16 group in cell medium was significantly higher that that of the control group (P<0.01). There was significant difference between the CXCL16 group and the RSG group (P<0.05).5. The model of vascular restenosis of rabbit iliac arteries were established successfully. The levels of serum TC, TG and LDL-C had significant difference between the model group and the RSG group (P<0.05). 6. Compared with the model group, intimal thickness (IT), the intimal area (IA), IT/MT ratio and IA/MA ratio of the RSG group were significantly decreased (P<0.01).7. RSG upregulated the protein expressions of PCNA, MMP-2 (P<0.05), but had no effect on TIMP-2 (P>0.05).Conclusions1. RSG can inhibit CXCL16-induced the proliferation of rat VSMCs.2. RSG can reduce CXCL16-induced Akt and NF-κB mRNA and protein overexpression in rat VSMCs.3. RSG can decrease the synthesis of TNF-αinduced by CXCL16.4. RSG can inhibit neointimal formation and attenuate vascular restenosis of rabbit iliac artery after balloon injury.5. RSG can interfere with cell generation cycle, decrease the ratio MMP-2 to TIMP-2, further inhibit the proliferation and migration in vascular restenosis of rabbits.Main creativitiesRSG possesses multi-target therapeutic effects, including inhibition of Akt/NF-κB pathway, down-regulation of CXCL16 expression and protection of aorta.
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