Author + information
- Received July 3, 2002
- Revision received January 8, 2003
- Accepted January 16, 2003
- Published online May 21, 2003.
- David Rott, MD*,
- Jianhui Zhu, MD, PhD*,
- Mary Susan Burnett, PhD*,
- Y.i F.u Zhou, MD*,
- Alexandra Zalles-Ganley, BS*,
- Jibike Ogunmakinwa, BS* and
- Stephen E Epstein, MD*,* ()
- ↵*Reprint requests and correspondence:
Dr. Stephen E. Epstein, Cardiovascular Research Institute, Washington Hospital Center, 110 Irving Street NW, Suite 4B-1, Washington, DC 20010, USA.
Objectives We examined whether selective cyclooxygenase-2 (COX-2) inhibition in apolipoprotein-E (apoE) deficient mice reduces cytomegalovirus (CMV) replication, and determined whether COX-2 anti-inflammatory activity leads to decreased atherosclerosis.
Background Evidence suggests that CMV infection contributes to atherosclerosis and that this occurs in part through inflammatory mechanisms. Cyclooxygenase-2 inhibitors are potent anti-inflammatory agents. They also inhibit CMV replication in vitro.
Methods The apoE deficient mice were either treated or not treated with a selective COX-2 inhibitor, and either infected or not infected with CMV. Viral deoxyribonucleic acid load in salivary glands was determined by quantitative polymerase chain reaction. Atherosclerotic lesion analysis was performed by standard methods.
Results In vivo COX-2 inhibition, unexpectedly increased viral load: in the CMV-infected animals viral load was 2.58 ± 1.0 in the nontreated group, 4.74 ± 1.38 in the group treated with 12 mg/kg/day MF-tricyclic, and 6.51 ± 1.64 in the group treated with 24 mg/kg/day MF-tricyclic (p trend = 0.050). This increased viral load was paralleled by increased anti-CMV antibody titers. Most surprisingly, COX-2 inhibition significantly increased early atherosclerotic lesion area, independent of viral infection.
Conclusions Our study demonstrates that selective inhibition of COX-2 in vivo increases viral load. The finding that inhibition of COX-2 increases atherosclerosis development in apoE deficient mice suggests, unexpectedly, that this enzyme exerts antiatherosclerosis activity, at least in this model.
☆ This work was supported in part by a grant from Merck Pharmaceuticals.
- Received July 3, 2002.
- Revision received January 8, 2003.
- Accepted January 16, 2003.
- American College of Cardiology Foundation