(Circulation. 1995;92:2995-3005.)
© 1995 American Heart Association, Inc.
Articles |
Vascular Injury, Repair, and Restenosis After Percutaneous Transluminal Angioplasty in the Atherosclerotic Rabbit
Presented in part at the 64th Scientific Sessions of the American Heart Association, Dallas, Tex, November 11-14, 1991, and the 41st Scientific Sessions of the American College of Cardiology, Dallas, Tex., March 1992.
From the Krannert Institute of Cardiology, Department of Medicine, Roudebush VA Medical Center, Indiana University School of Medicine and Eli Lilly and Co. (G.S.), Indianapolis, Ind.
Correspondence to Robert L. Wilensky, MD, Krannert Institute of Cardiology, 1111 W 10th St, Indianapolis, IN 46202-4800.
Background Several nonatherosclerotic animal models of restenosis exist and are used for the evaluation of the vascular response to angioplasty-induced injury. However, few studies have evaluated the response of an atherosclerotic vessel to angioplasty. The present study examined the radiographic, histological, immunohistochemical, and morphometric responses over time of atherosclerotic rabbit femoral arteries after percutaneous transluminal angioplasty (PTA).
Methods and Results Rabbits (n=94) underwent arterial desiccation and were fed a hypercholesterolemic diet for 3 weeks, and then PTA was performed. Arteries were obtained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused radial stretching of the artery, medial compression, intramural hemorrhage, injury to normal arterial segments, and dissection within the intima and media. Thrombus filled and cellular accumulation repaired the dissection. Peak smooth muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after angioplasty, generally at the dissection but also in normal sections of the artery. Adventitial injury and subsequent adventitial cellular proliferation and collagen production were observed. A rapid decrease in the radiographic minimal luminal diameter was noted at 3 days, resulting from vascular recoil or thrombus filling the dissection. At 7 to 14 days, only 24% to 33% of the luminal loss was accounted for by an increase in the intimal area, and 22% to 28% of the intima was neointima.
Conclusions Restenosis in an atherosclerotic artery results from a variable combination of intimal proliferation, vascular remodeling/wound contraction, and recoil of the normal section of the artery. The variability of an atherosclerotic artery to PTA injury results from variable dissection, thrombus formation, and cellular response to injury as well as variable scar contraction and elastic recoil.
Key Words: atherosclerosis • stenosis • remodeling • angioplasty
This article has been cited by other articles:
 |
|
 |
|
  L. E. Leigh Perkins Preclinical Models of Restenosis and Their Application in the Evaluation of Drug-Eluting Stent Systems Veterinary Pathology, January 1, 2010; 47(1): 58 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W. Q. Moore and D. Y. Hui Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase J. Lipid Res., October 1, 2005; 46(10): 2083 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Hofmann, C. P. Sullivan, H.-Y. Jiang, P. J. Stone, P. Toselli, E. D. Reis, I. Chereshnev, B. M. Schreiber, and G. E. Sonenshein B-Myb Represses Vascular Smooth Muscle Cell Collagen Gene Expression and Inhibits Neointima Formation After Arterial Injury Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1608 - 1613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W.Q. Moore, B. Zhu, D. G. Kuhel, and D. Y. Hui Vascular Apolipoprotein E Expression and Recruitment from Circulation to Modulate Smooth Muscle Cell Response to Endothelial Denudation Am. J. Pathol., June 1, 2004; 164(6): 2109 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Danenberg, F. G. P. Welt, M. Walker III, P. Seifert, G. S. Toegel, and E. R. Edelman Systemic Inflammation Induced by Lipopolysaccharide Increases Neointimal Formation After Balloon and Stent Injury in Rabbits Circulation, June 18, 2002; 105(24): 2917 - 2922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. M. Hassan, I. M. Lang, M. Ignatescu, R. Ullrich, D. Bonderman, P. Wexberg, F. Weidinger, and H. D. Glogar Increased intimal apoptosis in coronary atherosclerotic vessel segments lacking compensatory enlargement J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1333 - 1339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Kiesz, P. Buszman, J. L. Martin, E. Deutsch, M. M. Rozek, E. Gaszewska, M. Rewicki, P. Seweryniak, M. Kosmider, and M. Tendera Local Delivery of Enoxaparin to Decrease Restenosis After Stenting: Results of Initial Multicenter Trial : Polish-American Local Lovenox NIR Assessment Study (The POLONIA Study) Circulation, January 2, 2001; 103(1): 26 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Cottin, M. Kollum, R. Chan, B. Bhargava, Y. Vodovotz, and R. Waksman Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1389 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hou, P. I. Rogers, P. M. Toleikis, W. Hunter, and K. L. March Intrapericardial Paclitaxel Delivery Inhibits Neointimal Proliferation and Promotes Arterial Enlargement After Porcine Coronary Overstretch Circulation, September 26, 2000; 102(13): 1575 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Calderon, S. D. Gertz, I. J. Sarembock, J. A. Berliner, J. T. Fallon, M. B. Taubman, and J. W. Berman Induction of IG9 Monocyte Adhesion Molecule Expression in Smooth Muscle and Endothelial Cells After Balloon Arterial Injury in Cholesterol-Fed Rabbits Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1293 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Marso, A. M. Lincoff, S. G. Ellis, D. L. Bhatt, J.-F. Tanguay, N. S. Kleiman, T. Hammoud, J. E. Booth, S. K. Sapp, and E. J. Topol Optimizing the Percutaneous Interventional Outcomes for Patients With Diabetes Mellitus : Results of the EPISTENT (Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial) Diabetic Substudy Circulation, December 21, 1999; 100(25): 2477 - 2484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Okamura, M. Ohishi, H. Rakugi, T. Katsuya, Y. Yanagitani, S. Takiuchi, Y. Taniyama, K. Moriguchi, H. Ito, Y. Higashino, et al. Pharmacogenetic Analysis of the Effect of Angiotensin-Converting Enzyme Inhibitor on Restenosis After Percutaneous Transluminal Coronary Angioplasty Angiology, October 1, 1999; 50(10): 811 - 822. [Abstract] [PDF]
|
|
|
|
|
|
G. Plenz, A. Dorszewski, G. Breithardt, and H. Robenek Expression of Type VIII Collagen After Cholesterol Diet and Injury in the Rabbit Model of Atherosclerosis Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1201 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Meerkin, J.-C. Tardif, I. R. Crocker, A. Arsenault, M. Joyal, G. Lucier, S. B. King III, D. O. Williams, P. W. Serruys, and R. Bonan Effects of Intracoronary ß-Radiation Therapy After Coronary Angioplasty : An Intravascular Ultrasound Study Circulation, April 6, 1999; 99(13): 1660 - 1665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Le Tourneau, E. Van Belle, D. Corseaux, B. Vallet, G. Lebuffe, B. Dupuis, J.-M. Lablanche, E. McFadden, C. Bauters, and M. E. Bertrand Role of nitric oxide in restenosis after experimental balloon angioplasty in the hypercholesterolemic rabbit: effects on neointimal hyperplasia and vascular remodeling J. Am. Coll. Cardiol., March 1, 1999; 33(3): 876 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bosmans, C. J. Vrints, M. M. Kockx, H. Bult, K. M. C. Cromheeke, and A. G. Herman Continuous Perivascular L-Arginine Delivery Increases Total Vessel Area and Reduces Neointimal Thickening After Experimental Balloon Dilatation Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 767 - 776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Pels, M. Labinaz, C. Hoffert, and E. R. O'Brien Adventitial Angiogenesis Early After Coronary Angioplasty : Correlation With Arterial Remodeling Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 229 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R Bennett Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture Cardiovasc Res, February 1, 1999; 41(2): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Wilensky, K. Mehdi, K. M. Sowinski, Sang Hong Baek, and K. L. March Increased Intramural Retention After Local Delivery of Molecules with Increased Binding Properties: Implications for Regional Delivery of Pharmacologic Agents Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(2): 103 - 112. [Abstract] [PDF]
|
|
|
|
|
|
B. D. Klugherz, N. Meneveau, W. Chen, F. Wade-Whittaker, G. Papandreou, R. Levy, and R. L. Wilensky Sustained Intramural Retention and Regional Redistribution Following Local Vascular Delivery of Polylactic-Coglycolic Acid and Liposomal Nanoparticulate Formulations Containing Probucol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(3): 167 - 174. [Abstract] [PDF]
|
|
|
|
|
|
A. Lafont and D. Faxon Why do animal models of post-angioplasty restenosis sometimes poorly predict the outcome of clinical trials? Cardiovasc Res, July 1, 1998; 39(1): 50 - 59. [Full Text] [PDF]
|
|
|
|
|
|
M. Oberhoff, S. Novak, C. Herdeg, A. Baumbach, A. Kranzhofer, A. Bohnet, B. Horch, H. Hanke, K. K. Haase, and K. R. Karsch Local and systemic delivery of low molecular weight heparin stimulates the reendothelialization after balloon angioplasty Cardiovasc Res, June 1, 1998; 38(3): 751 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. W. Courtman, S. M. Schwartz, and C. E. Hart Sequential Injury of the Rabbit Abdominal Aorta Induces Intramural Coagulation and Luminal Narrowing Independent of Intimal Mass : Extrinsic Pathway Inhibition Eliminates Luminal Narrowing Circ. Res., May 19, 1998; 82(9): 996 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Baek and K. L. March Gene Therapy for Restenosis : Getting Nearer the Heart of the Matter Circ. Res., February 23, 1998; 82(3): 295 - 305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kumar, J. L. Hoover, C. A. Simmons, V. Lindner, and R. J. Shebuski Remodeling and Neointimal Formation in the Carotid Artery of Normal and P-Selectin–Deficient Mice Circulation, December 16, 1997; 96(12): 4333 - 4342. [Abstract] [Full Text]
|
|
|
|
|
|
S.D. Gertz, W. L Barry, L. W Gimple, Shmuel Banai, L. S Perez, C. A McNamara, E. R Powers, M. Ragosta, G. K Owens, W. C Roberts, et al. Predictors of luminal narrowing by neointima after angioplasty in atherosclerotic rabbits Cardiovasc Res, December 1, 1997; 36(3): 396 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Capron, J. Jarnet, D. Heudes, D. Joseph-Monrose, and P. Bruneval Repeated Balloon Injury of Rat Aorta : A Model of Neointima With Attenuated Inhibition by Heparin Arterioscler Thromb Vasc Biol, September 1, 1997; 17(9): 1649 - 1656. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ueno, H. Yamamoto, S.-i. Ito, J.-J. Li, and A. Takeshita Adenovirus-Mediated Transfer of a Dominant-Negative H-ras Suppresses Neointimal Formation in Balloon-Injured Arteries In Vivo Arterioscler Thromb Vasc Biol, May 1, 1997; 17(5): 898 - 904. [Abstract] [Full Text]
|
|
|
|
|
|
P. R. Moreno, V. H. Bernardi, J. Lopez-Cuellar, J. B. Newell, C. McMellon, H. K. Gold, I. F. Palacios, V. Fuster, and J. T. Fallon Macrophage Infiltration Predicts Restenosis After Coronary Intervention in Patients With Unstable Angina Circulation, December 15, 1996; 94(12): 3098 - 3102. [Abstract] [Full Text]
|
|