(Circulation. 2001;103:2980.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Effects of Balloon Injury on Neointimal Hyperplasia in Streptozotocin-Induced Diabetes and in Hyperinsulinemic Nondiabetic Pancreatic Islet–Transplanted Rats
From the Division of Cardiology (D.T., L.C., C.C., A.R., E.D., E.S., C.P., A.C., M.C.) and the Division of Internal Medicine (F.P.), University Federico II, and the National Cancer Institute (M.V.C.), Naples; Magna Graecia University, Catanzaro (C.I.); and the Unit of Metabolic Disease, Istituto Scientifico San Raffaele, Milan (A.D.), Italy; and the Department of Medicine, Duke University, Durham, NC (G.E.). The first 2 authors contributed equally to this study.
Correspondence to Ciro Indolfi, MD, FACC, FESC, Laboratory of Clinical and Experimental Interventional Cardiology, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy. E-mail indolfi{at}unina.it
Background—The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown.
Methods and Results—Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras–negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed.
Conclusions—In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals.
Key Words: diabetes mellitus • balloon • angioplasty • insulin
This article has been cited by other articles:
 |
|
 |
|
  D. M. Breen, K. K. Chan, J. K. Dhaliwall, M. R. Ward, N. Al Koudsi, L. Lam, M. De Souza, H. Ghanim, P. Dandona, D. J. Stewart, et al. Insulin Increases Reendothelialization and Inhibits Cell Migration and Neointimal Growth After Arterial Injury Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
N. Sasaki, T. Yamashita, T. Takaya, M. Shinohara, R. Shiraki, M. Takeda, N. Emoto, A. Fukatsu, T. Hayashi, K. Ikemoto, et al. Augmentation of Vascular Remodeling by Uncoupled Endothelial Nitric Oxide Synthase in a Mouse Model of Diabetes Mellitus Arterioscler Thromb Vasc Biol, June 1, 2008; 28(6): 1068 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Anan, T. Masaki, Y. Umeno, T. Iwao, H. Yonemochi, N. Eshima, T. Saikawa, and H. Yoshimatsu Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients Eur. J. Endocrinol., September 1, 2007; 157(3): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Torella, A. Curcio, C. Gasparri, V. Galuppo, D. D. Serio, F. C. Surace, A. L. Cavaliere, A. Leone, C. Coppola, G. M. Ellison, et al. Fludarabine prevents smooth muscle proliferation in vitro and neointimal hyperplasia in vivo through specific inhibition of STAT-1 activation Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2935 - H2943. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
T. Matsuoka, J. Wada, I. Hashimoto, Y. Zhang, J. Eguchi, N. Ogawa, K. Shikata, Y. S. Kanwar, and H. Makino Gene Delivery of Tim44 Reduces Mitochondrial Superoxide Production and Ameliorates Neointimal Proliferation of Injured Carotid Artery in Diabetic Rats Diabetes, October 1, 2005; 54(10): 2882 - 2890. [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. 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]
|
|
|
|
 |
|
 P. Fiorina, C. Gremizzi, P. Maffi, R. Caldara, D. Tavano, L. Monti, C. Socci, F. Folli, F. Fazio, E. Astorri, et al. Islet Transplantation Is Associated With an Improvement of Cardiovascular Function in Type 1 Diabetic Kidney Transplant Patients Diabetes Care, June 1, 2005; 28(6): 1358 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Sengstock, P. V. Vaitkevicius, and M. A. Supiano Arterial Stiffness Is Related to Insulin Resistance in Nondiabetic Hypertensive Older Adults J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2823 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakazawa, T. Chiba, E. Kaneko, K. Yui, M. Yoshida, and K. Shimokado Insulin Signaling in Arteries Prevents Smooth Muscle Apoptosis Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 760 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhuang, A.-C. Ceacareanu, B. Ceacareanu, and A. Hassid Essential role of protein kinase G and decreased cytoplasmic Ca2+ levels in NO-induced inhibition of rat aortic smooth muscle cell motility Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1859 - H1866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Torella, D. Leosco, C. Indolfi, A. Curcio, C. Coppola, G. M. Ellison, V. G. Russo, M. Torella, G. L. Volti, F. Rengo, et al. Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2850 - H2860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhuang, A.-C. Ceacareanu, Y. Lin, B. Ceacareanu, M. Dixit, K. E. Chapman, C. M. Waters, G. N. Rao, and A. Hassid Nitric oxide attenuates insulin- or IGF-I-stimulated aortic smooth muscle cell motility by decreasing H2O2 levels: essential role of cGMP Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2103 - H2112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Curcio, D. Torella, G. Cuda, C. Coppola, M. C. Faniello, F. Achille, V. G. Russo, M. Chiariello, and C. Indolfi Effect of stent coating alone on in vitro vascular smooth muscle cell proliferation and apoptosis Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H902 - H908. [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]
|
|
|
|
|
|
M. Dixit, D. Zhuang, B. Ceacareanu, and A. Hassid Treatment With Insulin Uncovers the Motogenic Capacity of Nitric Oxide in Aortic Smooth Muscle Cells: Dependence on Gab1 and Gab1-SHP2 Association Circ. Res., November 14, 2003; 93 (10): e113 - e123. [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]
|
|
|
|
|
|
C. Indolfi, D. Torella, C. Coppola, A. Curcio, F. Rodriguez, A. Bilancio, A. Leccia, O. Arcucci, M. Falco, D. Leosco, et al. Physical Training Increases eNOS Vascular Expression and Activity and Reduces Restenosis After Balloon Angioplasty or Arterial Stenting in Rats Circ. Res., December 13, 2002; 91(12): 1190 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Indolfi, D. Torella, C. Coppola, E. Stabile, G. Esposito, A. Curcio, A. Pisani, L. Cavuto, O. Arcucci, M. Cireddu, et al. Rat carotid artery dilation by PTCA balloon catheter induces neointima formation in presence of IEL rupture Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H760 - H767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sreejayan, Y. Lin, and A. Hassid NO Attenuates Insulin Signaling and Motility in Aortic Smooth Muscle Cells via Protein Tyrosine Phosphatase 1B-Mediated Mechanism Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Indolfi Genetic factors in atherosclerosis: status and perspectives Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B14 - B16. [Abstract] [PDF]
|
|