doi: 10.1161/hc3301.092789
(Circulation. 2001;104:815.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Neointimal Hyperplasia After Arterial Injury Is Increased in a Rat Model of Non–Insulin-Dependent Diabetes Mellitus
From the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio (S.P., Z.Z., F.F., E.J.T., A.M.L.), and Mid America Heart Institute, Saint Luke’s Hospital, Kansas City, Mo (S.P.M.).
Correspondence to A. Michael Lincoff, MD, Department of Cardiology, F25, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195-5066.
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.
Methods and 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 mm2, 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 mm2, 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.
Key Words: diabetes mellitus • restenosis • insulin • angioplasty
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