|Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Object: The present study was designed to clarify the effect of treatment with herpes simplex virus (HSV) inhibited vascular smooth muscle cell proliferation on vasospasm with atherosclerosis.
Methods: We produced a prolonged vasospasm model of Kurosawa and Kusanagi- hypercholesterolemic rabbit common carotid artery by applying a blood-filled silicone sheet around the vessel. A HSV vector, d12CALP, in which the calponin promoter drives ICP4 gene and thymidine kinase promoter drives LacZ gene (1×10^9 pfu/ml) was administered into the right common carotid artery on Days 0, 1 and 2 (HSV-treated groups). Calponin is well-known protein which is specifically expressed in smooth muscle cells, therefore d12CALP replicates in and destroy well dividing smooth muscle cells alone. After perfusion -fixation of each rabbits on Day 7, the common carotid arteries treated with HSV were stained with X-gal to detect the distribution of virus replication. Morphometric analysis including measurements of lum
inal area and wall thickness was also performed.
Results: In HSV-treated on Day 2 group, smooth muscle cells in the carotid artery revealed positive staining with X-gal. However, there was no blue staining in HSV-treated on Days 0 and 1 groups. Morphometric analysis demonstrated a marked reduction in the luminal area as well as increase in the wall thickness on Day 2 in HSV-no treated group. These changes were significantly persistent on Day 7. In all HSV-treated groups, however, there was no constriction of the vessel and it was dilated rather, compared to the control group. Especially, in HSV-treated on Day 2 group, the degree of vasodilatation was significantly strong (P<0.01).
Conclusion: In a vasospasm model of common carotid artery with atherosclerosis, vascular smooth muscle proliferation was developed on Day 2. Therefore, we considered that inhibition of the vascular smooth muscle cell proliferation at this time by HSV might provide a novel approach for the treatment of vasospasm. Less