Effects of probucol on rat carotid artery responses to balloon catheter injury.
Balloon catheter injury to the rat common carotid artery has been widely used for testing potential therapies for post-angioplasty restenosis. However, the model has become somewhat discredited because a number of drugs that inhibit intimal thickening, measured 14 days after balloon catheter injury, have been found to be ineffective in clinical trials. Probucol has recently been shown to reduce the incidence of post-angioplasty restenosis in a number of small clinical trials, making it possible to reassess the validity of the rat balloon injury model. The effects of probucol on the underlying causes of intimal thickening in balloon-injured rat carotid arteries were quantified. Probucol inhibited medial smooth muscle cell proliferation by 23% on day 4 after injury (P=0.009), and by 65% on day 10 after injury (P=0.026). Smooth muscle cell migration was reduced by 64% (P=0.008) in probucol-treated animals. In marked contrast, intimal smooth muscle cell proliferation was significantly increased by 41% (P=0.024) by probucol. There was no significant effect on intimal thickening or smooth muscle cell death. These data suggest that drugs that inhibit both medial smooth muscle cell proliferation and migration in the rat balloon injury model may prove useful in the treatment of post-angioplasty restenosis.
Jackson
C L
CL
Bristol Heart Institute, British Royal Infirmary, Level 7, University of Bristol, BS2 8HW, Bristol, UK.
Pettersson
K S
KS
D000284:Administration, Oral; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004032:Diet; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D011341:Probucol / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015203:Reproducibility of Results; D055502:Secondary Prevention; D017539:Tunica Intima / Q000187:drug effects / Q000293:injuries / Q000473:pathology
D000924:Anticholesteremic Agents; D011341:Probucol