Inhibition of intimal hyperplasia in transgenic mice conditionally expressing the chemokine-binding protein M3.
Chemokines have been implicated in the pathogenesis of a wide variety of diseases. This report describes the generation of transgenic mice that conditionally express M3, a herpesvirus protein that binds and inhibits chemokines. In response to doxycycline, M3 expression was induced in a variety of tissues and M3 was detectable in the blood by Western blotting. No gross or histological abnormalities were seen in mice expressing M3. To determine whether M3 expression could modify a significant pathophysiological response, we examined its effect on the development of intimal hyperplasia in response to femoral arterial injury. Intimal hyperplasia is thought to play a critical role in the development of restenosis after percutaneous transluminal coronary angioplasty and in the progression of atherosclerosis. Induction of M3 expression resulted in a 67% reduction in intimal area and a 68% reduction in intimal/medial ratio after femoral artery injury. These data support a role for chemokines in regulating intimal hyperplasia and suggest that M3 may be effective in attenuating this process. This transgenic mouse model should be a valuable tool for investigating the role of chemokines in a variety of pathological states.
Pyo
Robert
R
Department of Medicine, and the Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Jensen
Kristian K
KK
Wiekowski
Maria T
MT
Manfra
Denise
D
Alcami
Antonio
A
Taubman
Mark B
MB
Lira
Sergio A
SA
D000818:Animals; D001774:Blood Chemical Analysis; D004318:Doxycycline / Q000494:pharmacology; D005263:Femoral Artery / Q000473:pathology; D015967:Gene Expression Regulation, Viral; D006965:Hyperplasia / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D017539:Tunica Intima / Q000473:pathology*; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics
C118862:M3 protein, Murine gammaherpesvirus; D014764:Viral Proteins; D001616:beta-Galactosidase; D004318:Doxycycline