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
This article has been cited by other articles:
 |
|
 |
|
  Q. Pu, Y. Chang, C. Zhang, Y. Cai, and A. Hassid Chronic insulin treatment suppresses PTP1B function, induces increased PDGF signaling, and amplifies neointima formation in the balloon-injured rat artery Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H132 - H139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhuang, Q. Pu, B. Ceacareanu, Y. Chang, M. Dixit, and A. Hassid Chronic insulin treatment amplifies PDGF-induced motility in differentiated aortic smooth muscle cells by suppressing the expression and function of PTP1B Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H163 - H173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bruemmer C-Peptide in Insulin Resistance and Vascular Complications: Teaching an Old Dog New Tricks Circ. Res., November 24, 2006; 99(11): 1149 - 1151. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wang, Z. Zhou, M. Zhang, L. Fan, F. Forudi, X. Zhou, W. Qu, A. M. Lincoff, A. M. Schmidt, E. J. Topol, et al. Peroxisome Proliferator-Activated Receptor {gamma} Down-Regulates Receptor for Advanced Glycation End Products and Inhibits Smooth Muscle Cell Proliferation in a Diabetic and Nondiabetic Rat Carotid Artery Injury Model J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 37 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Srivastava, K. V. Ramana, R. Tammali, S. K. Srivastava, and A. Bhatnagar Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells. Diabetes, April 1, 2006; 55(4): 901 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Chang, B. Ceacareanu, D. Zhuang, C. Zhang, Q. Pu, A. C. Ceacareanu, and A. Hassid Counter-Regulatory Function of Protein Tyrosine Phosphatase 1B in Platelet-Derived Growth Factor- or Fibroblast Growth Factor-Induced Motility and Proliferation of Cultured Smooth Muscle Cells and in Neointima Formation Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 501 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pei, J. Gu, P.-R. Thimmalapura, A. Mison, and J. L. Nadler Activation of the 12-lipoxygenase and signal transducer and activator of transcription pathway during neointima formation in a model of the metabolic syndrome Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E92 - E102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jonas, E. R. Edelman, A. Groothuis, A. B. Baker, P. Seifert, and C. Rogers Vascular Neointimal Formation and Signaling Pathway Activation in Response to Stent Injury in Insulin-Resistant and Diabetic Animals Circ. Res., September 30, 2005; 97(7): 725 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Barbato, B. S. Zuckerbraun, M. Overhaus, K. G. Raman, and E. Tzeng Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H228 - H236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Molnar, S. Yu, N. Mzhavia, C. Pau, I. Chereshnev, and H. M. Dansky Diabetes Induces Endothelial Dysfunction but Does Not Increase Neointimal Formation in High-Fat Diet Fed C57BL/6J Mice Circ. Res., June 10, 2005; 96(11): 1178 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nishimatsu, E. Suzuki, H. Satonaka, R. Takeda, M. Omata, T. Fujita, R. Nagai, T. Kitamura, and Y. Hirata Endothelial dysfunction and hypercontractility of vascular myocytes are ameliorated by fluvastatin in obese Zucker rats Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1770 - H1776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Takeda, E. Suzuki, H. Satonaka, S. Oba, H. Nishimatsu, M. Omata, T. Fujita, R. Nagai, and Y. Hirata Blockade of Endogenous Cytokines Mitigates Neointimal Formation in Obese Zucker Rats Circulation, March 22, 2005; 111(11): 1398 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Naka, L. G. Bucciarelli, T. Wendt, L. K. Lee, L. L. Rong, R. Ramasamy, S. F. Yan, and A. M. Schmidt RAGE Axis: Animal Models and Novel Insights Into the Vascular Complications of Diabetes Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1342 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Desouza, S. N. Murthy, J. Diez, B. Dunne, A. S. Matta, V. A. Fonseca, and D. B. McNamara Differential Effects of Peroxisome Proliferator Activator Receptor-{alpha} and {gamma} Ligands on Intimal Hyperplasia After Balloon Catheter-Induced Vascular Injury in Zucker Rats Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2003; 8(4): 297 - 305. [Abstract] [PDF]
|
|
|
|
|
|
K. Stephenson, J. Tunstead, A. Tsai, R. Gordon, S. Henderson, and H. M. Dansky Neointimal Formation After Endovascular Arterial Injury Is Markedly Attenuated in db/db Mice Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 2027 - 2033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. I. Stenina, I. Krukovets, K. Wang, Z. Zhou, F. Forudi, M. S. Penn, E. J. Topol, and E. F. Plow Increased Expression of Thrombospondin-1 in Vessel Wall of Diabetic Zucker Rat Circulation, July 1, 2003; 107(25): 3209 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Mak and D. P. Faxon Clinical studies on coronary revascularization in patients with type 2 diabetes Eur. Heart J., June 2, 2003; 24(12): 1087 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, K. Wang, M. S. Penn, S. P. Marso, M. A. Lauer, F. Forudi, X. Zhou, W. Qu, Y. Lu, D. M. Stern, et al. Receptor for AGE (RAGE) Mediates Neointimal Formation in Response to Arterial Injury Circulation, May 6, 2003; 107(17): 2238 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Uwatoku, H. Shimokawa, K. Abe, Y. Matsumoto, T. Hattori, K. Oi, T. Matsuda, K. Kataoka, and A. Takeshita Application of Nanoparticle Technology for the Prevention of Restenosis After Balloon Injury in Rats Circ. Res., April 18, 2003; 92 (7): e62 - e69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, M. S. Penn, F. Forudi, X. Zhou, K. Tarakji, E. J. Topol, A. M. Lincoff, and K. Wang Administration of Recombinant P-Selectin Glycoprotein Ligand Fc Fusion Protein Suppresses Inflammation and Neointimal Formation in Zucker Diabetic Rat Model Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1598 - 1603. [Abstract] [Full Text] [PDF]
|
|