Neointimal hyperplasia after arterial injury is increased in a rat model of non-insulin-dependent diabetes mellitus.
BACKGROUND
The key biological determinants that promote restenosis in the setting of diabetes have not been elucidated. There is no accepted animal model to study restenosis in diabetes.


RESULTS
We evaluated 2 models of diabetes mellitus: (1) streptozotocin (STZ)-treated Sprague-Dawley rats (type I diabetes) versus regular Sprague-Dawley rats and (2) obese Zucker rats (type II diabetes) versus lean Zucker rats. Neointimal hyperplasia was assessed after carotid balloon injury at 21 days by computerized morphometry. There was no difference in neointimal area in the STZ-treated rats compared with controls, irrespective of insulin administration or dose of STZ. Neointimal area was increased >2-fold in obese Zucker rats compared with lean Zucker rats (0.21+/-0.06 versus 0.08+/-0.03 mm(2), P<0.01). The neointimal area was markedly increased in the obese Zucker rats 7 days after injury (0.058+/-0.024 versus 0.033+/-0.009 mm(2), P<0.05) and persisted through 21 days. In both obese and lean Zucker rats, cell proliferation peaked in the media at 3 days (118.66+/-84.28 versus 27.50+/-12.75 bromodeoxyuridine-labeled cells per cross section). In the intima, cell proliferation markedly increased beginning at day 3 and persisted through day 14 in the obese and lean Zucker rats (202.27+/-98.86 versus 35.71+/-20.54 bromodeoxyuridine-labeled cells at 7 days).


CONCLUSIONS
The type II diabetic rat model, typifying insulin resistance, is associated with a propensity for neointima. The obese Zucker rat model may be an ideal diabetic model to further characterize the diabetic vascular response to injury.
Park
S H
SH
Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195-5066, USA.
Marso
S P
SP
Zhou
Z
Z
Foroudi
F
F
Topol
E J
EJ
Lincoff
A M
AM
D000818:Animals; D001973:Bromodeoxyuridine; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D002452:Cell Count; D002455:Cell Division; D003920:Diabetes Mellitus / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D009765:Obesity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*; D014654:Vascular Patency
D001973:Bromodeoxyuridine