Effect of herpes simplex virus vector, d12CALP, on vasospasm in rabbit common carotid artery with atherosclerotic changes

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Osaka Medical College
• Principal Investigator: TAMURA Yoji Osaka Medical College Faculty of Medicine Research Associate, 医学部, 助手 (90247859)
• Co-Investigator(Kenkyū-buntansha): KUROIWA Toshihiko Osaka Medical College Faculty of Medicine Professor, 医学部, 教授 (30178115) ; MIYATAKE Shinichi Osaka Medical College Faculty of Medicine Associate Professor, 医学部, 助教授 (90209916)
• Project Period (FY): 2001 – 2002
• Keywords: vasospasm / atherosclerosis / KHC rabbit / common carotid artery / herpes simplex virus / vascular smooth muscle cell / calponin

Research Abstract

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.