(Circulation. 2001;103:882.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Mechanisms of Neointima Formation and Remodeling in the Porcine Coronary Artery
From Department of Pathology, University of Geneva-CMU (T.C., M.-L.B.-P., G.G.), and the Divisions of Cardiology (V.V., P.D., E.C.) and Radiotherapy (Y.P.), University Hospital Geneva, Geneva, Switzerland; and the Department of Molecular Cell Biology and Genetics, University of Maastricht, Maastricht, Netherlands (G.v.E., F.R.).
Background—To characterize the cells responsible for neointima formation after porcine coronary artery wall injury, we studied the expression of smooth muscle cell (SMC) differentiation markers in 2 models: (1) self-expanding stent implantation resulting in no or little interruption of internal elastic lamina and (2) percutaneous transluminal coronary angioplasty (PTCA) resulting in complete medial rupture and exposure of adventitia to blood components.
Methods and Results—The
expression of 
-smooth muscle (SM) actin, SM myosin heavy chain
isoforms 1 and 2, desmin, and smoothelin was investigated by means of
immunohistochemistry and Western blots in tissues of the arterial wall
collected at different time points and in cell populations cultured
from these tissues. The expression of smoothelin, a marker of late SMC
differentiation, was used to discriminate between SMCs and
myofibroblasts. Both stent- and PTCA-induced neointimal tissues and
their cultured cell populations expressed all 4 markers. The
adventitial tissue underlying PTCA-induced lesions temporarily
expressed -SM actin, desmin, and SM myosin heavy chain isoforms, but
not smoothelin. When placed in culture, adventitial cells expressed
only -SM actin.
Conclusions—Our results suggest that SMCs are the main components of coronary artery neointima after both self-expanding stent implantation and PTCA. The adventitial reaction observed after PTCA evolves with a chronology independent of that of neointima formation and probably corresponds to a myofibroblastic reaction.
Key Words: angioplasty • stents • muscle, smooth • myofibroblasts • smoothelin
This article has been cited by other articles:
 |
|
 |
|
  T. Higo, Y. Ueda, J. Oyabu, K. Okada, M. Nishio, A. Hirata, K. Kashiwase, N. Ogasawara, S. Hirotani, and K. Kodama Atherosclerotic and thrombogenic neointima formed over sirolimus drug-eluting stent an angioscopic study. J. Am. Coll. Cardiol. Img., May 1, 2009; 2(5): 616 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Fleenor and D. K. Bowles Negligible contribution of coronary adventitial fibroblasts to neointimal formation following balloon angioplasty in swine Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1532 - H1539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Rensen, P. M. Niessen, J. M. van Deursen, B. J. Janssen, E. Heijman, E. Hermeling, M. Meens, N. Lie, M. J. Gijbels, G. J. Strijkers, et al. Smoothelin-B Deficiency Results in Reduced Arterial Contractility, Hypertension, and Cardiac Hypertrophy in Mice Circulation, August 19, 2008; 118(8): 828 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Chadjichristos, S. Morel, J.-P. Derouette, E. Sutter, I. Roth, A. C. Brisset, M.-L. Bochaton-Piallat, and B. R. Kwak Targeting Connexin 43 Prevents Platelet-Derived Growth Factor-BB-Induced Phenotypic Change in Porcine Coronary Artery Smooth Muscle Cells Circ. Res., March 28, 2008; 102(6): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Borensztajn, J. Stiekema, S. Nijmeijer, P. H. Reitsma, M. P. Peppelenbosch, and C. A. Spek Factor Xa Stimulates Proinflammatory and Profibrotic Responses in Fibroblasts via Protease-Activated Receptor-2 Activation Am. J. Pathol., February 1, 2008; 172(2): 309 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C.M. Siow and A. T. Churchman Adventitial growth factor signalling and vascular remodelling: Potential of perivascular gene transfer from the outside-in Cardiovasc Res, September 1, 2007; 75(4): 659 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Brisset, H. Hao, E. Camenzind, M. Bacchetta, A. Geinoz, J.-C. Sanchez, C. Chaponnier, G. Gabbiani, and M.-L. Bochaton-Piallat Intimal Smooth Muscle Cells of Porcine and Human Coronary Artery Express S100A4, a Marker of the Rhomboid Phenotype In Vitro Circ. Res., April 13, 2007; 100(7): 1055 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Clempus, D. Sorescu, A. E. Dikalova, L. Pounkova, P. Jo, G. P. Sorescu, B. Lassegue, and K. K. Griendling Nox4 Is Required for Maintenance of the Differentiated Vascular Smooth Muscle Cell Phenotype Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 42 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Collison, A. Agarwal, and N. Trehan Controversies in the use of intraluminal shunts during off-pump coronary artery bypass grafting surgery. Ann. Thorac. Surg., October 1, 2006; 82(4): 1559 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Gorenne, L. Jin, T. Yoshida, J.M. Sanders, I.J. Sarembock, G.K. Owens, A.P. Somlyo, and A.V. Somlyo LPP Expression During In Vitro Smooth Muscle Differentiation and Stent-Induced Vascular Injury Circ. Res., February 17, 2006; 98(3): 378 - 385. [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. Fujiu, I. Manabe, A. Ishihara, Y. Oishi, H. Iwata, G. Nishimura, T. Shindo, K. Maemura, H. Kagechika, K. Shudo, et al. Synthetic Retinoid Am80 Suppresses Smooth Muscle Phenotypic Modulation and In-Stent Neointima Formation by Inhibiting KLF5 Circ. Res., November 25, 2005; 97(11): 1132 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Spencer, S. L. Hacker, E. C. Davis, R. P. Mecham, R. H. Knutsen, D. Y. Li, R. D. Gerard, J. A. Richardson, E. N. Olson, and H. Yanagisawa Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration PNAS, February 22, 2005; 102(8): 2946 - 2951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. B. Hangler, K. Pfaller, E. Ruttmann, D. Hoefer, T. Schachner, G. Laufer, and H. Antretter Effects of intracoronary shunts on coronary endothelial coating in the human beating heart Ann. Thorac. Surg., March 1, 2004; 77(3): 776 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Skowasch, A. Jabs, R. Andrie, S. Dinkelbach, B. Luderitz, and G. Bauriedel Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis Cardiovasc Res, December 1, 2003; 60(3): 684 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bauriedel, A. Jabs, D. Skowasch, R. Hutter, J. J. Badimon, V. Fuster, U. Welsch, and B. Luderitz Dendritic cells in neointima formation after rat carotid balloon injury: coordinated expression withanti-apoptotic Bcl-2 and HSP47 in arterial repair J. Am. Coll. Cardiol., September 3, 2003; 42(5): 930 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C.M Siow, C. M Mallawaarachchi, and P. L Weissberg Migration of adventitial myofibroblasts following vascular balloon injury: insights from in vivo gene transfer to rat carotid arteries Cardiovasc Res, July 1, 2003; 59(1): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zalewski, Y. Shi, and A. G. Johnson Diverse Origin of Intimal Cells: Smooth Muscle Cells, Myofibroblasts, Fibroblasts, and Beyond? Circ. Res., October 18, 2002; 91(8): 652 - 655. [Full Text] [PDF]
|
|
|
|
|
|
P. Verhamme, R. Quarck, H. Hao, M. Knaapen, S. Dymarkowski, H. Bernar, J. Van Cleemput, S. Janssens, J. Vermylen, G. Gabbiani, et al. Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Cardiovasc Res, October 1, 2002; 56(1): 135 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Theilmeier, R. Quarck, P. Verhamme, M.-L. Bochaton-Piallat, M. Lox, H. Bernar, S. Janssens, M. Kockx, G. Gabbiani, D. Collen, et al. Hypercholesterolemia impairs vascular remodelling after porcine coronary angioplasty Cardiovasc Res, August 1, 2002; 55(2): 385 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hao, P. Ropraz, V. Verin, E. Camenzind, A. Geinoz, M. S. Pepper, G. Gabbiani, and M.-L. Bochaton-Piallat Heterogeneity of Smooth Muscle Cell Populations Cultured From Pig Coronary Artery Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1093 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Maehara, N. S. Patel, L. B. Harrison, N. J. Weissman, A. B. Bui, H.-S. Kim, A. E. Ajani, M. T. Castagna, T. L. McMillan, N. Yang, et al. Dose heterogeneity may not affect the neointimal proliferation after gamma radiation for in-stent restenosis: A volumetric intravascular ultrasound dosimetric study J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1937 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Szocs, B. Lassegue, D. Sorescu, L. L. Hilenski, L. Valppu, T. L. Couse, J. N. Wilcox, M. T. Quinn, J.D. Lambeth, and K. K. Griendling Upregulation of Nox-Based NAD(P)H Oxidases in Restenosis After Carotid Injury Arterioscler Thromb Vasc Biol, January 1, 2002; 22(1): 21 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Castagna, G. S. Mintz, R. Waksman, J. M. Ahmed, A. Maehara, A. E. Ajani, A. B. Bui, L. F. Satler, W. O. Suddath, K. M. Kent, et al. Comparative Efficacy of {gamma}-Irradiation for Treatment of In-Stent Restenosis in Saphenous Vein Graft Versus Native Coronary Artery In-Stent Restenosis: An Intravascular Ultrasound Study Circulation, December 18, 2001; 104(25): 3020 - 3022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sartore, A. Chiavegato, E. Faggin, R. Franch, M. Puato, S. Ausoni, and P. Pauletto Contribution of Adventitial Fibroblasts to Neointima Formation and Vascular Remodeling: From Innocent Bystander to Active Participant Circ. Res., December 7, 2001; 89(12): 1111 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Miller Jr Adventitial Fibroblasts : Backstage Journeymen Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 722 - 723. [Full Text] [PDF]
|
|