Inhibition of leucocyte and platelet adhesion reduces neointimal hyperplasia after arterial injury.
Restenosis following coronary angioplasty is though to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD11/CD18 adhesion complex, aurintricarboxylic acid (ATA), a substance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 +/- 0.07 mm2 in control animals and it was significantly reduced by administration of either R15.7 or ATA alone to 0.12 +/- 0.05 and 0.20 +/- 0.01 mm2, respectively (p < 0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p < 0.05 vs ATA alone). These data indicate that platelets and leucocytes play an important role in the pathophysiology of neointimal hyperplasia in this experimental model. Interventions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.
Golino
P
P
Department of Internal Medicine, 2nd School of Medicine, University of Naples, Italy.
Ambrosio
G
G
Ragni
M
M
Cirillo
P
P
Esposito
N
N
Willerson
J T
JT
Rothlein
R
R
Petrucci
L
L
Condorelli
M
M
Chiariello
M
M
Buja
L M
LM
D000818:Animals; D000911:Antibodies, Monoclonal; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D018845:CD11 Antigens / Q000097:blood; D018821:CD18 Antigens / Q000097:blood; D016893:Carotid Stenosis / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000293:injuries*; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D010973:Platelet Adhesiveness / Q000502:physiology*; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000097:blood; D017539:Tunica Intima / Q000473:pathology*
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D001312:Aurintricarboxylic Acid