Attenuated herpes simplex virus 1 blocks arterial apoptosis and intimal hyperplasia induced by balloon angioplasty and reduced blood flow

doi:10.1073/pnas.0705429104

Attenuated herpes simplex virus 1 blocks arterial apoptosis and intimal hyperplasia induced by balloon angioplasty and reduced blood flow

*Section of Vascular Surgery, Department of Surgery,
^‡Department of Radiation and Cellular Oncology, and
^§Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637

Contributed by Bernard Roizman, June 9, 2007 (received for review May 24, 2007)

Abstract

Injury caused by distention of the arterial wall by balloon angioplasty can result in apoptosis and vascular smooth muscle cell proliferation. Here, we report that a brief exposure of the arterial lumen to a genetically engineered, attenuated herpes simplex virus 1 blocks activation of caspase 3-dependent apoptosis and MAPK-dependent cell proliferation induced by carotid artery balloon angioplasty and ligation to reduce blood flow. The procedure enables the restoration of the endothelial cell layer lining the lumen and prevents neointimal hyperplasia and restenosis. These findings have a broad application in prevention of balloon angioplasty-induced restenosis.

Footnotes

^†To whom correspondence may be addressed at:
Section of Vascular Surgery, Department of Surgery, University of Chicago, MC 5028, 5841 South Maryland Avenue, Chicago, IL 60637.
E-mail: cskelly{at}surgery.bsd.uchicago.edu
^¶To whom correspondence may be addressed. E-mail: bernard.roizman{at}bsd.uchicago.edu
Author contributions: C.L.S., R.R.W., and B.R. designed research; C.L.S., A.C., and J.E.V. performed research; R.R.W. and B.R. contributed new reagents/analytic tools; C.L.S. and R.R.W. analyzed data; and C.L.S. and B.R. wrote the paper.
The authors declare no conflict of interest.
↵ ‖ Cadoz, M., Micoud, M., Seigneurim, J. M., Mallert, M. R., Baccard, C., Moranbd, P., 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, October 11–14, 1992, Anaheim, CA.
Abbreviations:

HSV-1,

herpes simplex virus 1;

PCNA,

proliferating cell nuclear antigen;

CCA,

common carotid artery.