Intimal hyperplasia, an abnormal migration and proliferation of vascular smooth muscle cells with associated deposition of extracellular connective tissue matrix, is a chronic structual changes occuring in denuded arteries, arterialized vein and prosthetic bypass graft. This is one of the most important cause of vascular graft failure within the first year after operation. Certain growth factors, particularly basic fibroblast growth factor, transforming growth factor- , and platelet-derived growth factor, are believed to be the cause of the smooth muscle cell proliferation and migration. This smooth muscle cell proliferation and collagen deposition eventually produce intimal thickening with subsequent stenosis or occlusion of the vascular lumen. In order to evaluate the serial changes of injured vessel wall, aortic patch allograft was done in rat, and studied the morphological finding at 1 day, 1, 2, 6, and 8 weeks after graft. The results were summerized as follows; (1) During the early phase after graft, no significant wall changes were seen in the region of the anastomotic site except the presence of acute inflammatory cells with platelet aggregation and thrombus formation. (2) The intimal thickening was apparent by 1 week and was predominantly composed of smooth muscle cells. At the 2 weeks after graft, endothelial cells were partially regenerated to cover the patch graft, and intimal hyperplasia was composed of a mixture of smooth muscle cells and extracellular matrix, mostly collagen. (3) Six weeks after graft, prominent features were production and deposition of collagen rather than proliferation of smooth muscle cells. Reendothelialization over the thickened intima was seen at 8 weeks and the propagation of intimal hyperplasia to adjacent intima of normal vessel was also noted. In conclusion, intimal hyperplasia after vascular injury seemed to be a progressive response of the proliferation and migration of smooth muscle cells and this result might be used for further study about the suppression of intimal hyperplasia.
Allografts ; Animals ; Aorta ; Arteries ; Collagen ; Connective Tissue ; Constriction, Pathologic ; Endothelial Cells ; Extracellular Matrix ; Fibroblast Growth Factor 2 ; Hyperplasia ; Intercellular Signaling Peptides and Proteins ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Platelet Aggregation ; Platelet-Derived Growth Factor ; Rats ; Thrombosis ; Transplants ; Vascular System Injuries ; Veins

BACKGROUND: The effects of diallyl disulfide (DADS), a garlic derived compound, on the viability and cell signaling- like the downstream signaling through cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP) during an oxidative-stress induced injury were studied using H2O2 treated neuronal-differentiated PC12 cells by a nerve growth factor. METHODS: To evaluate the toxicity of the DADS itself, the viability of the differentiated PC12 cells treated with several concentrations of DADS was evaluated with 3, (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. To evaluate the protective effect of the low concentration of DADS from oxidative stress, the viability of the cells (DADS pretreated vs. not pretreated) was evaluated following the exposure to 100 micro M H2O2. Additionally, the expression of caspase-3, PARP, and cytochrome c was examined using western blot analyses. RESULTS: The viability was not affected at low concentrations of DADS, up to 20 micro M, but, over this concentration, it was decreased. Compared with the cells treated with only 100 micro M H2O2, the pretreatment with low concentrations of DADS before exposure to 100 micro M H2O2 increased the viability and induced the inhibition of caspase-3 activation, PARP cleavage, and cytochrome c release. CONCLUSIONS: These results show that low concentrations of DADS shows neuroprotective effects by affecting the downstream signaling through cytochrome c, caspase-3, and PARP pathway and may be a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury.
Animals ; Apoptosis* ; Blotting, Western ; Caspase 3 ; Cytochromes c ; Cytochromes* ; Garlic ; Nerve Growth Factor ; Neurodegenerative Diseases ; Neuroprotective Agents ; Oxidative Stress ; PC12 Cells*