© 1996 American Heart Association, Inc.
Articles |
Time Course of Cellular Proliferation, Intimal Hyperplasia, and Remodeling Following Angioplasty in Monkeys With Established Atherosclerosis
A Nonhuman Primate Model of Restenosis
From the Departments of Surgery (R.L.G., D.G.B., M.E.B.) and Comparative Medicine (J.K.W., D.G., M.R.A.), The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.
Correspondence to Randolph L. Geary, MD, Division of Surgical Sciences, Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1095. E-mail rgeary@isnet.is.wfu.edu.
Abstract Animal models of arterial injury have failed to predict effective therapy to prevent restenosis in humans. While this may relate to species differences in the control of smooth muscle cell growth, many studies have used nonatherosclerotic animals, thereby failing to consider the importance of atherosclerosis in the response to injury. In an attempt to model human restenosis more accurately, we characterized the response to angioplasty in atherosclerotic monkeys. Twenty-one cynomolgus monkeys were fed an atherogenic diet for 36 months (plasma cholesterol, 12±1 mmol/L [470±23 mg/dL]). Angioplasty was then performed in the left iliac artery. After 4, 7, 14, or 28 days, bromodeoxyuridine was given to label proliferating cells, and iliac arteries were fixed in situ at physiological pressure (5 or 6 animals at each time point). Comparisons were made between injured and uninjured iliac arteries within each animal. Angioplasty often fractured the intimal plaque and media, transiently increasing lumen caliber (4 days: lumen area, 232.5±80.3% of control) and artery size as reflected by external elastic lamina area (EEL). EEL and lumen caliber returned to baseline by 7 days. Proliferation was increased throughout the artery wall at 4 and 7 days and later declined to control rates (4 days, injured versus uninjured: adventitia, 45.0±6.2% versus 16.3±7.2%; media, 8.6±2.6% versus 0.6±0.1%; intima, 16.0±5.6% versus 7.8±3.1%). The intima thickened markedly from 14 to 28 days, but an increase in EEL generally prevented further loss of the short-term gain in lumen caliber (28 days, percent of control: intimal area, 342.8±88.9%; EEL area, 150.2±28.9%; lumen area, 119.3±21.3%). The response to angioplasty in atherosclerotic monkeys appears to closely resemble that in humans. Plaque fracture, delayed recoil, intimal hyperplasia, and remodeling may each be important in determining late lumen caliber. This primate model should prove valuable in defining cellular and biochemical mediators of human restenosis.
Key Words: angioplasty • remodeling • restenosis • cellular proliferation • Macaca fascicularis
This article has been cited by other articles:
 |
|
 |
|
  T.A. Abruzzo, F.C. Tong, A.S.M. Waldrop, M.J. Workman, H.J. Cloft, and J.E. Dion Basilar Artery Stent Angioplasty for Symptomatic Intracranial Athero-Occlusive Disease: Complications and Late Midterm Clinical Outcomes AJNR Am. J. Neuroradiol., May 1, 2007; 28(5): 808 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Touchard and R. S. Schwartz Preclinical Restenosis Models: Challenges and Successes Toxicol Pathol, January 1, 2006; 34(1): 11 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Masuo, T. Terada, G. Walker, M. Tsuura, K. Nakai, and T. Itakura Patency of Perforating Arteries after Stent Placement? A Study Using an In Vivo Experimental Atherosclerosis-Induced Model AJNR Am. J. Neuroradiol., March 1, 2005; 26(3): 543 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Farb, F. D. Kolodgie, J.-Y. Hwang, A. P. Burke, K. Tefera, D. K. Weber, T. N. Wight, and R. Virmani Extracellular Matrix Changes in Stented Human Coronary Arteries Circulation, August 24, 2004; 110(8): 940 - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Taurin, V. Seyrantepe, S. N. Orlov, T.-L. Tremblay, P. Thibault, M. R. Bennett, P. Hamet, and A. V. Pshezhetsky Proteome Analysis and Functional Expression Identify Mortalin as an Antiapoptotic Gene Induced by Elevation of [Na+]i/[K+]i Ratio in Cultured Vascular Smooth Muscle Cells Circ. Res., November 15, 2002; 91(10): 915 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pasterkamp, M. J. Sierevogel, D. P.V. de Kleijn, B. H. Strauss, R. L. Geary, and G. S. Cherr MMP Inhibition and Lumen Loss After Balloon Angioplasty or Stenting * In Response Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1241 - 1241. [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Lowe, S. N. Oesterle, and L. M. Khachigian Coronary in-stent restenosis: Current status and future strategies J. Am. Coll. Cardiol., January 16, 2002; 39(2): 183 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Cherr, S. J. Motew, J. A. Travis, J. Fingerle, L. Fisher, M. Brandl, J. K. Williams, and R. L. Geary Metalloproteinase Inhibition and the Response to Angioplasty and Stenting in Atherosclerotic Primates Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 161 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Andres, J. Urena, E. Poch, D. Chen, and D. Goukassian Role of Sp1 in the Induction of p27 Gene Expression in Vascular Smooth Muscle Cells In Vitro and After Balloon Angioplasty Arterioscler Thromb Vasc Biol, March 1, 2001; 21(3): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Adams, R. L. Geary, B. McManus, and S. M. Schwartz A Comparison of Aorta and Vena Cava Medial Message Expression by cDNA Array Analysis Identifies a Set of 68 Consistently Differentially Expressed Genes, All in Aortic Media Circ. Res., September 29, 2000; 87(7): 623 - 631. [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]
|
|
|
|
 |
|
 L. Wu, P. Chen, J.-J. Hwang, L. W. Barsky, K. I. Weinberg, A. Jong, and V. A. Starnes RNA Antisense Abrogation of MAT1 Induces G1 Phase Arrest and Triggers Apoptosis in Aortic Smooth Muscle Cells J. Biol. Chem., February 26, 1999; 274(9): 5564 - 5572. [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]
|
|
|
|
|
|
J. S. Deitch, J. K. Williams, M. R. Adams, C. A. Fly, D. M. Herrington, R. E. Jordan, M. T. Nakada, J. A. Jakubowski, and R. L. Geary Effects of ß3-Integrin Blockade (c7E3) on the Response to Angioplasty and Intra-Arterial Stenting in Atherosclerotic Nonhuman Primates Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1730 - 1737. [Abstract] [Full Text] [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]
|
|
|
|
|
|
H. Di Wang, P. J. Pagano, Y. Du, A. J. Cayatte, M. T. Quinn, P. Brecher, and R. A. Cohen Superoxide Anion From the Adventitia of the Rat Thoracic Aorta Inactivates Nitric Oxide Circ. Res., April 20, 1998; 82(7): 810 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Holvoet, G. Theilmeier, B. Shivalkar, W. Flameng, and D. Collen LDL Hypercholesterolemia Is Associated With Accumulation of Oxidized LDL, Atherosclerotic Plaque Growth, and Compensatory Vessel Enlargement in Coronary Arteries of Miniature Pigs Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 415 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-I Yeh, F. Lupu, E. Dupont, and N. J. Severs Upregulation of Connexin43 Gap Junctions Between Smooth Muscle Cells After Balloon Catheter Injury in the Rat Carotid Artery Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3174 - 3184. [Abstract] [Full Text]
|
|
|
|
|
|
A. L. Wong, Z. A. Haroon, S. Werner, M. W. Dewhirst, C. S. Greenberg, and K. G. Peters Tie2 Expression and Phosphorylation in Angiogenic and Quiescent Adult Tissues Circ. Res., October 19, 1997; 81(4): 567 - 574. [Abstract] [Full Text]
|
|
|
|
|
|
W. D. Coats, P. Whittaker, D. T. Cheung, J. W. Currier, B. Han, and D. P. Faxon Collagen Content Is Significantly Lower in Restenotic Versus Nonrestenotic Vessels After Balloon Angioplasty in the Atherosclerotic Rabbit Model Circulation, March 4, 1997; 95(5): 1293 - 1300. [Abstract] [Full Text]
|
|