(Circulation. 1997;95:981-987.)
© 1997 American Heart Association, Inc.
Articles |
Evidence for the Rapid Onset of Apoptosis in Medial Smooth Muscle Cells After Balloon Injury
the Division of Cardiovascular Research, St Elizabeth's Medical Center, Tufts University School of Medicine (H.P., L.M., K.K, K.W.), and the Program in Cell, Molecular, and Developmental Biology, Sackler School of Biomedical Sciences, Tufts University (H.P., K.W.), Boston, Mass.
Correspondence to Kenneth Walsh, Division of Cardiovascular Research, St Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135-2997. E-mail kwalsh@opal.tufts.edu.
Background Vascular myocyte apoptotic cell death has been reported in human atherectomy and endarterectomy specimens and for neointimal smooth muscle cells (SMCs) in balloon-injured rat carotid arteries between 7 and 30 days after injury. However, the immediate effect of balloon injury on medial SMC viability has not been examined.
Methods and Results Rat carotid arteries were harvested at the time of balloon injury (T=0) and at 0.5, 1, 2, and 4 hours after injury. Uninjured vessels or vessels harvested at the time of injury (T=0) did not display evidence of apoptosis. However, as early as 30 minutes after injury, 70% of medial SMCs appeared apoptotic by TdT-mediated dUTP nick end labeling (TUNEL) analysis and by the appearance of condensed chromatin. High frequencies of TUNEL-positive cells were also observed at 1 and 2 hours after injury but not at 4 hours. Transmission electron microscopy revealed many cells with morphological characteristics of apoptosis in the injured sections. A marked decrease in bcl-X expression was detected in the most luminal layers of the media. To corroborate these findings in a second animal model, rabbit external iliac arteries were analyzed after balloon angioplasty. Apoptotic cell death was evident in rabbit arteries at 30 minutes and at 4 hours after injury.
Conclusions As early as 30 minutes after balloon injury, myocytes appear to undergo apoptotic cell death at a high frequency as shown by TUNEL staining, chromatin condensation, and the appearance of morphological features in electron micrographs. The induction of apoptosis coincides with a marked downregulation of bcl-X expression.
Key Words: balloon • apoptosis • angioplasty • muscle, smooth • remodeling
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P. J. M. Best, D. Hasdai, G. Sangiorgi, R. S. Schwartz, D. R. Holmes Jr, R. D. Simari, and A. Lerman Apoptosis : Basic Concepts and Implications in Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 14 - 22. [Abstract] [Full Text] [PDF]
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M. M. Kockx Apoptosis in the Atherosclerotic Plaque : Quantitative and Qualitative Aspects Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1519 - 1522. [Abstract] [Full Text] [PDF]
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J. M. Miano, L. A. Kelly, C. A. Artacho, T. A. Nuckolls, R. Piantedosi, and W. S. Blaner all-Trans-Retinoic Acid Reduces Neointimal Formation and Promotes Favorable Geometric Remodeling of the Rat Carotid Artery After Balloon Withdrawal Injury Circulation, September 22, 1998; 98(12): 1219 - 1227. [Abstract] [Full Text] [PDF]
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A. Haunstetter and S. Izumo Apoptosis : Basic Mechanisms and Implications for Cardiovascular Disease Circ. Res., June 15, 1998; 82(11): 1111 - 1129. [Full Text] [PDF]
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S. Kim, Y. Izumi, M. Yano, A. Hamaguchi, K. Miura, S. Yamanaka, H. Miyazaki, and H. Iwao Angiotensin Blockade Inhibits Activation of Mitogen-Activated Protein Kinases in Rat Balloon-Injured Artery Circulation, May 5, 1998; 97(17): 1731 - 1737. [Abstract] [Full Text] [PDF]
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J. E. O'Brien Jr, M. L. Ormont, Y. Shi, D. Wang, A. Zalewski, and J. D. Mannion Early Injury to the Media After Saphenous Vein Grafting Ann. Thorac. Surg., May 1, 1998; 65(5): 1273 - 1278. [Abstract] [Full Text] [PDF]
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H. Wang and J. A. Keiser Molecular characterization of rabbit CPP32 and its function in vascular smooth muscle cell apoptosis Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1132 - H1140. [Abstract] [Full Text] [PDF]
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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]
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 M. Sata, H. Perlman, D. A. Muruve, M. Silver, M. Ikebe, T. A. Libermann, P. Oettgen, and K. Walsh Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response PNAS, February 3, 1998; 95(3): 1213 - 1217. [Abstract] [Full Text] [PDF]
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H. Yaoita, K. Ogawa, K. Maehara, and Y. Maruyama Attenuation of Ischemia/Reperfusion Injury in Rats by a Caspase Inhibitor Circulation, January 27, 1998; 97(3): 276 - 281. [Abstract] [Full Text] [PDF]
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E. T.H. Yeh Life and Death in the Cardiovascular System Circulation, February 18, 1997; 95(4): 782 - 786. [Full Text]
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