Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries.
BACKGROUND
P-selectin plays key roles in mediating inflammation through promoting adherence of leukocytes to activated platelets and endothelium. This process is one of the initial events in atherosclerosis and restenosis after coronary angioplasty.


RESULTS
Using a rat balloon-injury model, we examined the role of P-selectin in vascular inflammatory processes. In the acute phase, immunohistochemistry revealed that P-selectin was intensely expressed on both activated platelets covering the denuded segment and endothelial cells of the inflamed adventitial small vessels. Treatment with an anti-P-selectin monoclonal antibody (MAb) for 8 consecutive days significantly inhibited neointimal formation at day 14 (42% inhibition; P:<0.05), and this effect persisted at day 56 (40% inhibition; P:<0.01) compared with the control group. Vascular shrinking accompanying adventitial fibrosis was also attenuated at day 56. Inhibition of both neointimal formation and vascular shrinking resulted in the lumen area of the anti-P-selectin treatment group being approximately 3 times larger at day 56 than that of the control group. Accumulation of CD45-positive leukocytes in the developing neointima, media, and adventitia at day 8 was significantly inhibited by treatment with the anti-P-selectin MAb. Scanning electron microscopy demonstrated that anti-P-selectin treatment resulted in a less thrombogenic surface of the arterial intima, which featured a pseudoendothelial appearance at day 14 after injury.


CONCLUSIONS
These results suggest that inhibition of P-selectin-mediated leukocyte recruitment prevents the development of neointimal formation, adventitial inflammation, and vascular shrinking and promotes pseudoendothelialization by luminal smooth muscle cells. This treatment thus beneficially affects vascular remodeling after balloon injury in rats.
Hayashi
S
S
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Watanabe
N
N
Nakazawa
K
K
Suzuki
J
J
Tsushima
K
K
Tamatani
T
T
Sakamoto
S
S
Isobe
M
M
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000911:Antibodies, Monoclonal; D016466:CHO Cells; D016893:Carotid Stenosis / Q000209:etiology* / Q000473:pathology; D006224:Cricetinae; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008297:Male; D019007:P-Selectin / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection; D017539:Tunica Intima / Q000473:pathology*; D014657:Vasculitis / Q000209:etiology*
D000911:Antibodies, Monoclonal; D019007:P-Selectin