This is the Scientific Surgery Archive, which contains all randomized clinical trials in surgery that have been identified by searching the top 50 English language medical journal issues since January 1998. Compiled by Jonothan J. Earnshaw, former Editor-in-Chief, BJS
Reduction of vascular smooth muscle cell proliferation by immunomodulation. BJS 2001; 88: 614-614.
Published: 6th December 2002
Authors: Y. C. Chan, N. Shukla, D. O. Okonko, M. Singh, J. L. Stanford, A. O. Mansfield et al.
Background
Immunological factors may play an important role in mediating the progression of atherosclerosis and myointimal hyperplasia, with heat shock proteins being implicated as possible autoantigens. The authors have shown previously that immunomodulation can reduce vascular smooth muscle cell (vSMC) proliferation following balloon injury to rat carotid arteries. The aim of the present study was to examine the effects of immunomodulatory agents on the proliferation of rat aortic vSMCs remote from the area of balloon injury. The agents used were SRL172 (heat‐killed Mycobacterium vaccae) and heat shock protein 65 kDa (HSP65) in Freund's incomplete adjuvant. Both these agents are known to influence T‐cell responses.
Method
Male Sprague–Dawley rats were used. All immunizations were given subcutaneously. Four groups were studied (ten animals in each group): group 1 animals were immunized with normal saline, group 2 received SRL172, group 3 SRL172 and HSP65–Freund's, and group 4 HSP65–Freund's. Three immunizations were performed as well as carotid balloon injury. Three animals died, leaving 37 for analysis. Some 5 weeks later the animals were killed and the aorta was harvested. Standard explant techniques were applied to grow aortic vSMCs until confluency, passaged three times, quiesced, and fetal calf serum (FCS) of varying concentrations (0·4–10 per cent) was then added, incubated for another 48 h and cell counts carried out.
Results
The proliferation rate of aortic vSMCs in the control group was significantly greater than that in the other study groups (Fig.). While all the treatment groups had significantly less proliferation compared with the control group (*P < 0·05, †P < 0·01, Mann–Whitney U test), no statistically significant differences existed between any of the study groups.
Conclusion
Immunomodulation may result in a reduction of vSMC proliferation. Although the precise mechanisms involved are unclear, these results are in concordance with previous findings that T‐cell immunomodulation decreases the development of myointimal hyperplasia after injury, and suggest that a fundamental phenotypic shift has been produced by these immunizations.
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