| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:2974.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC.
Correspondence to Renu Virmani, MD, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000. E-mail Virmani{at}afip.osd.mil
Background Experimental studies suggest that arterial injury and inflammation lead to increased neointimal growth after stenting. Despite the increased use of coronary stents in humans, there are only limited pathological data on the morphological features of in-stent restenosis.
Methods and Results Detailed histology was performed on 116 stents, implanted
90 days in 87 coronary arteries, from 56 patients (mean age, 59±13 years). The mean duration of stent implant was 10 months. In-stent restenosis was defined as a stent area stenosis of >75%. Lumen area increased as stent area increased (r2=0.27, P=0.0001), but there was a much stronger correlation between stent area and neointimal area (r2=0.70, P<0.0001). Arterial medial fracture was associated with a 29% increase (P<0.01) in neointimal thickness compared with arteries with an intact media. Neointimal thickness (P=0.0001), inflammatory cell density (P<0.0001), and neointimal vascular channel density (P<0.0001) were greater when struts were in contact with a ruptured arterial media compared with fibrous plaque or an intact fibrous cap. Stent strut penetration into a lipid core was associated with increased neointimal thickness (P=0.04) and inflammatory cell density (P=0.03). Neointimal inflammatory cell content was 2.4-fold greater in stents with restenosis versus no restenosis, and inflammation was associated with increased neoangiogenesis.
Conclusions Coronary stenting that is accompanied by medial damage or penetration of the stent into a lipid core induces increased arterial inflammation, which is associated with increased neointimal growth. These data suggest the use of stenting strategies that reduce inflammation and neoangiogenesis to reduce the incidence of restenosis.
Key Words: stents restenosis atherosclerosis pathology
This article has been cited by other articles:
![]() |
G. Nakazawa, A. V. Finn, M. Joner, E. Ladich, R. Kutys, E. K. Mont, H. K. Gold, A. P. Burke, F. D. Kolodgie, and R. Virmani Delayed Arterial Healing and Increased Late Stent Thrombosis at Culprit Sites After Drug-Eluting Stent Placement for Acute Myocardial Infarction Patients: An Autopsy Study Circulation, September 9, 2008; 118(11): 1138 - 1145. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Jimenez-Valero, R. Moreno, A. Sanchez-Recalde, G. Galeote, L. Calvo, A. Viana, E. Lopez de Sa, and J. Lopez-Sendon Review: Avoiding restenosis: is there a role for glucocorticoids in the drug-eluting stent era? Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 137 - 146. [Abstract] [PDF] |
||||
![]() |
J. Aoki, G. S. Mintz, N. J. Weissman, J. T. Mann, L. Cannon, J. Greenberg, E. Grube, A.R. Z. Masud, J. Koglin, L. Mandinov, et al. Chronic Arterial Responses to Overlapping Paclitaxel-Eluting Stents: Insights From Serial Intravascular Ultrasound Analyses in the TAXUS-V and -VI Trials J. Am. Coll. Cardiol. Intv., April 1, 2008; 1(2): 161 - 167. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. E. Hellings, F. L. Moll, J.-P. P.M. de Vries, P. de Bruin, D. P.V. de Kleijn, and G. Pasterkamp Histological Characterization of Restenotic Carotid Plaques in Relation to Recurrence Interval and Clinical Presentation: A Cohort Study Stroke, March 1, 2008; 39(3): 1029 - 1032. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. E. Hellings, F. L. Moll, J.-P. P. M. De Vries, R. G. A. Ackerstaff, K. A. Seldenrijk, R. Met, E. Velema, W. J. M. Derksen, D. P. V. De Kleijn, and G. Pasterkamp Atherosclerotic Plaque Composition and Occurrence of Restenosis After Carotid Endarterectomy JAMA, February 6, 2008; 299(5): 547 - 554. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. G. Nuhrenberg, N. Langwieser, J. B.K. Schwarz, Y. Hou, P. Frank, F. Sorge, S. Matschurat, S. Seidl, A. Kastrati, A. Schomig, et al. EMAP-II downregulation contributes to the beneficial effects of rapamycin after vascular injury Cardiovasc Res, February 1, 2008; 77(3): 580 - 589. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. V. Finn, G. Nakazawa, M. Joner, F. D. Kolodgie, E. K. Mont, H. K. Gold, and R. Virmani Vascular Responses to Drug Eluting Stents: Importance of Delayed Healing Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1500 - 1510. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. V. Finn, M. Joner, G. Nakazawa, F. Kolodgie, J. Newell, M. C. John, H. K. Gold, and R. Virmani Pathological Correlates of Late Drug-Eluting Stent Thrombosis: Strut Coverage as a Marker of Endothelialization Circulation, May 8, 2007; 115(18): 2435 - 2441. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. A. Ali, N. J. Alp, H. Lupton, N. Arnold, T. Bannister, Y. Hu, S. Mussa, M. Wheatcroft, D. R. Greaves, J. Gunn, et al. Increased In-Stent Stenosis in ApoE Knockout Mice: Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 833 - 840. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ohtani, K. Egashira, K. Nakano, G. Zhao, K. Funakoshi, Y. Ihara, S. Kimura, R. Tominaga, R. Morishita, and K. Sunagawa Stent-Based Local Delivery of Nuclear Factor-{kappa}B Decoy Attenuates In-Stent Restenosis in Hypercholesterolemic Rabbits Circulation, December 19, 2006; 114(25): 2773 - 2779. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ohtani, K. Egashira, Y. Ihara, K. Nakano, K. Funakoshi, G. Zhao, M. Sata, and K. Sunagawa Angiotensin II Type 1 Receptor Blockade Attenuates In-Stent Restenosis by Inhibiting Inflammation and Progenitor Cells Hypertension, October 1, 2006; 48(4): 664 - 670. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Jonas, J. C. Fang, J. C. Wang, S. Giri, D. Elian, Y. Har-Zahav, H. Ly, P. A. Seifert, J. J. Popma, and C. Rogers In-Stent Restenosis and Remote Coronary Lesion Progression Are Coupled in Cardiac Transplant Vasculopathy But Not in Native Coronary Artery Disease J. Am. Coll. Cardiol., August 1, 2006; 48(3): 453 - 461. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Joner, A. V. Finn, A. Farb, E. K. Mont, F. D. Kolodgie, E. Ladich, R. Kutys, K. Skorija, H. K. Gold, and R. Virmani Pathology of Drug-Eluting Stents in Humans: Delayed Healing and Late Thrombotic Risk J. Am. Coll. Cardiol., July 4, 2006; 48(1): 193 - 202. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. J. Gomes and E. Buffolo Coronary stenting and inflammation: implications for further surgical and medical treatment. Ann. Thorac. Surg., May 1, 2006; 81(5): 1918 - 1925. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Naruko, M. Ueda, S. Ehara, A. Itoh, K. Haze, N. Shirai, Y. Ikura, M. Ohsawa, H. Itabe, Y. Kobayashi, et al. Persistent High Levels of Plasma Oxidized Low-Density Lipoprotein After Acute Myocardial Infarction Predict Stent Restenosis Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 877 - 883. [Abstract] [Full Text] [PDF] |
||||
![]() |
A K Mitra and D K Agrawal In stent restenosis: bane of the stent era. J. Clin. Pathol., March 1, 2006; 59(3): 232 - 239. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.A. Boisvert, D.M. Rose, A. Boullier, O. Quehenberger, A. Sydlaske, K.A Johnson, L.K. Curtiss, and R. Terkeltaub Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size Arterioscler. Thromb. Vasc. Biol., March 1, 2006; 26(3): 563 - 569. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Varga, M. Eriksson, M. R. Erdos, M. Olive, I. Harten, F. Kolodgie, B. C. Capell, J. Cheng, D. Faddah, S. Perkins, et al. Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson-Gilford progeria syndrome PNAS, February 28, 2006; 103(9): 3250 - 3255. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Hao, G. Gabbiani, E. Camenzind, M. Bacchetta, R. Virmani, and M.-L. Bochaton-Piallat Phenotypic Modulation of Intima and Media Smooth Muscle Cells in Fatal Cases of Coronary Artery Lesion Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 326 - 332. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. J. Salu, J. M. Bosmans, Y. Huang, M. Hendriks, M. Verhoeven, A. Levels, S. Cooper, I. K. De Scheerder, C. J. Vrints, and H. Bult Effects of cytochalasin D-eluting stents on intimal hyperplasia in a porcine coronary artery model Cardiovasc Res, February 1, 2006; 69(2): 536 - 544. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. C. Henry, M. M. Bonar, P. N. Kearns, H. Cui, M. M. Mutchler, M. V. Martin, A. R. Orsini, H. L. Elford, C. A. Bush, J. L. Zweier, et al. Inhibition of Ribonucleotide Reductase Reduces Neointimal Formation following Balloon Injury J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 70 - 76. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Pache, A. Dibra, J. Mehilli, J. Dirschinger, A. Schomig, and A. Kastrati Drug-eluting stents compared with thin-strut bare stents for the reduction of restenosis: a prospective, randomized trial Eur. Heart J., July 1, 2005; 26(13): 1262 - 1268. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF] |
||||
![]() |
S. P. Lownie, D. M. Pelz, D. H. Lee, S. Men, I. Gulka, and P. Kalapos Efficacy of Treatment of Severe Carotid Bifurcation Stenosis By Using Self-Expanding Stents without Deliberate Use of Angioplasty Balloons AJNR Am. J. Neuroradiol., May 1, 2005; 26(5): 1241 - 1248. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. F. LaDisa Jr., Lars. E. Olson, R. C. Molthen, D. A. Hettrick, P. F. Pratt, M. D. Hardel, J. R. Kersten, D. C. Warltier, and P. S. Pagel Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2465 - H2475. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. W. Clowes Circulating Monocytes and In-Stent Neointima After Coronary Stent Implantation Perspectives in Vascular Surgery and Endovascular Therapy, March 1, 2005; 17(1): 60-1 - 62. [Abstract] [PDF] |
||||
![]() |
J. F. LaDisa Jr., L. E. Olson, I. Guler, D. A. Hettrick, J. R. Kersten, D. C. Warltier, and P. S. Pagel Circumferential vascular deformation after stent implantation alters wall shear stress evaluated with time-dependent 3D computational fluid dynamics models J Appl Physiol, March 1, 2005; 98(3): 947 - 957. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Koch, J. Mehilli, A. Pfeufer, A. Schomig, and A. Kastrati Apolipoprotein E gene polymorphisms and thrombosis and restenosis after coronary artery stenting J. Lipid Res., December 1, 2004; 45(12): 2221 - 2226. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Toutouzas, A. Colombo, and C. Stefanadis Inflammation and restenosis after percutaneous coronary interventions Eur. Heart J., October 1, 2004; 25(19): 1679 - 1687. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Z.H. Rittersma, R. J. de Winter, K. T. Koch, C. E. Schotborgh, M. Bax, G. S. Heyde, J. P. van Straalen, K. J. Mulder, J. G.P. Tijssen, G. T. Sanders, et al. Preprocedural C-Reactive Protein Is Not Associated with Angiographic Restenosis or Target Lesion Revascularization after Coronary Artery Stent Placement Clin. Chem., September 1, 2004; 50(9): 1589 - 1596. [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. W. Lindemann, C. C. Yost, M. M. Denis, T. M. McIntyre, A. S. Weyrich, and G. A. Zimmerman Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs PNAS, May 4, 2004; 101(18): 7076 - 7081. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Zohlnhofer, T. G. Nuhrenberg, F.-J. Neumann, T. Richter, A. E. May, R. Schmidt, K. Denker, M. A. Clauss, A. Schomig, and P. A. Baeuerle Rapamycin Effects Transcriptional Programs in Smooth Muscle Cells Controlling Proliferative and Inflammatory Properties Mol. Pharmacol., April 1, 2004; 65(4): 880 - 889. [Abstract] [Full Text] |
||||
![]() |
Z. Chen, M. Sakuma, A. C. Zago, X. Zhang, C. Shi, L. Leng, Y. Mizue, R. Bucala, and D. I. Simon Evidence for a Role of Macrophage Migration Inhibitory Factor in Vascular Disease Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 709 - 714. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. H Chong and J. W. Cheng Early Experiences and Clinical Implications of Drug-Eluting Stents: Part 1 Ann. Pharmacother., April 1, 2004; 38(4): 661 - 669. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Virmani, G. Guagliumi, A. Farb, G. Musumeci, N. Grieco, T. Motta, L. Mihalcsik, M. Tespili, O. Valsecchi, and F. D. Kolodgie Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent: Should We Be Cautious? Circulation, February 17, 2004; 109(6): 701 - 705. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. L. Johnson, L. M. Schofield, D. K. Weber, F. Kolodgie, R. Virmani, and B. A. Khaw Uptake of 111In-Z2D3 on SPECT Imaging in a Swine Model of Coronary Stent Restenosis Correlated with Cell Proliferation J. Nucl. Med., February 1, 2004; 45(2): 294 - 299. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Kornowski and S. Fuchs Optimization of glycemic control and restenosis prevention in diabetic patients undergoing percutaneous coronary interventions J. Am. Coll. Cardiol., January 7, 2004; 43(1): 15 - 17. [Full Text] [PDF] |
||||
![]() |
A. Colombo and G. Sangiorgi The monocyte: the key in the lock to reduce stent hyperplasia? J. Am. Coll. Cardiol., January 7, 2004; 43(1): 24 - 26. [Full Text] [PDF] |
||||
![]() |
Y.-H. Chen, L.-Y. Chau, M.-W. Lin, L.-C. Chen, M.-H. Yo, J.-W. Chen, and S.-J. Lin Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting Eur. Heart J., January 1, 2004; 25(1): 39 - 47. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Matsumoto, T. Uwatoku, K. Oi, K. Abe, T. Hattori, K. Morishige, Y. Eto, Y. Fukumoto, K.-i. Nakamura, Y. Shibata, et al. Long-Term Inhibition of Rho-Kinase Suppresses Neointimal Formation After Stent Implantation in Porcine Coronary Arteries: Involvement of Multiple Mechanisms Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 181 - 186. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Kereiakes Adjunctive Pharmacotherapy before Percutaneous Coronary Intervention in Non-ST-Elevation Acute Coronary Syndromes: The Role of Modulating Inflammation Circulation, October 21, 2003; 108(90161): III-22 - 27. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Farb, A. P. Burke, F. D. Kolodgie, and R. Virmani Pathological Mechanisms of Fatal Late Coronary Stent Thrombosis in Humans Circulation, October 7, 2003; 108(14): 1701 - 1706. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Kereiakes, A. M. Szyniszewski, D. Wahr, H. C. Herrmann, D. I. Simon, C. Rogers, P. Kramer, W. Shear, A. C. Yeung, K. A. Shunk, et al. Phase I Drug and Light Dose-Escalation Trial of Motexafin Lutetium and Far Red Light Activation (Phototherapy) in Subjects With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention and Stent Deployment: Procedural and Long-Term Results Circulation, September 16, 2003; 108(11): 1310 - 1315. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. K. Shah Inflammation, Neointimal Hyperplasia, and Restenosis: As the Leukocytes Roll, the Arteries Thicken Circulation, May 6, 2003; 107(17): 2175 - 2177. [Full Text] [PDF] |
||||
![]() |
D. F. Denny Jr Prediction of Restenosis after Carotid Artery Stent Implantation Radiology, May 1, 2003; 227(2): 316 - 318. [Full Text] [PDF] |
||||
![]() |
K. Egashira Molecular Mechanisms Mediating Inflammation in Vascular Disease: Special Reference to Monocyte Chemoattractant Protein-1 Hypertension, March 1, 2003; 41(3): 834 - 841. [Abstract] [Full Text] [PDF] |
||||
![]() |
R Virmani, F D Kolodgie, A Farb, and A Lafont Drug eluting stents: are human and animal studies comparable? Heart, February 1, 2003; 89(2): 133 - 138. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. J. Schoen and R. F. Padera Jr. Cardiac Surgical Pathology Card. Surg. Adult, January 1, 2003; 2(2003): 119 - 185. [Full Text] |
||||
![]() |
M. N. Babapulle and M. J. Eisenberg Coated Stents for the Prevention of Restenosis: Part I Circulation, November 19, 2002; 106(21): 2734 - 2740. [Full Text] [PDF] |
||||
![]() |
F. G.P. Welt and C. Rogers Inflammation and Restenosis in the Stent Era Arterioscler. Thromb. Vasc. Biol., November 1, 2002; 22(11): 1769 - 1776. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Weyrich, S. M. Prescott, and G. A. Zimmerman Platelets, Endothelial Cells, Inflammatory Chemokines, and Restenosis: Complex Signaling in the Vascular Play Book Circulation, September 17, 2002; 106(12): 1433 - 1435. [Full Text] [PDF] |
||||
![]() |
J. E. Sousa, M. A. Costa, and A. G.M.R. Sousa What Is "The Matter" With Restenosis in 2002? Circulation, June 25, 2002; 105(25): 2932 - 2933. [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2002 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |