Local administration of carbon monoxide inhibits neointima formation in balloon injured rat carotid arteries.
Recent studies indicate that systemic induction of heme oxygenase-1 (HO-1), which oxidatively degrades heme into iron, biliverdin, and carbon monoxide (CO), or adenoviral-mediated gene transfer of HO-1 inhibits neointima formation after experimental vascular injury. In the present study, we investigated whether the acute, local administration of the HO-1 product, CO, regulates the arterial remodeling response following injury. Immediately after balloon injury of rat carotid arteries, a saturated solution of CO or nitrogen (N2), or phosphate buffered saline (PBS) was incubated luminally within the injured vessels for 30 min. Two weeks after injury, arteries exposed to CO exhibited significantly reduced neointimal area, neointimal area/medial wall area ratio, neointimal thickness, and medial wall area compared to arteries exposed to N2 or PBS. Arteries exposed to CO also demonstrated significantly reduced DNA synthesis in the medial wall two days after injury as suggested by proliferating cell nuclear antigen immunostaining, and this was associated with a decrease in the protein expression of the G1 cyclins, cyclin E and A, and transforming growth factor-beta1. These results indicate that the acute, local delivery of CO blocks the pathophysiological remodeling response to vascular injury, and identifies CO as a potentially important therapeutic agent in the treatment of vasculoproliferative disease.
Tulis
D A
DA
Cardiovascular Disease Research Program, J.L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, North Carolina 27707, USA.
Keswani
A N
AN
Peyton
K J
KJ
Wang
H
H
Schafer
A I
AI
Durante
W
W
D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D020212:Carotid Artery Injuries / Q000628:therapy*; D002404:Catheterization / Q000009:adverse effects*; D016213:Cyclins / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000187:drug effects
D016213:Cyclins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002248:Carbon Monoxide; D004247:DNA