© 2001 American Heart Association, Inc.
Vascular Biology |
Mast Cell Chymase Induces Apoptosis of Vascular Smooth Muscle Cells
From the Wihuri Research Institute (M.L., Y.W., K.A.L., P.T.K.) and the STUK-Radiation and Nuclear Safety Authority (D.L.), Helsinki, Finland.
Correspondence to Petri T. Kovanen, MD, PhD, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland. E-mail petri.kovanen{at}wri.fi
Abstract—In human coronary atheromas, the numbers of degranulated mast cells and of apoptotic smooth muscle cells (SMCs) are increased. Accordingly, the possibility exists that mast cells participate in the regulation of SMC apoptosis in the lesions. Mast cells isolated from the serosal cavities of rats were stimulated to release their secretory granules. The neutral protease chymase, present in the exocytosed granules, was found to induce apoptosis when added to rat aortic SMCs in culture. The chymase-induced apoptosis of SMCs was detected by flow cytometry, microscopic analysis of cellular morphology, terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL), and electrophoretic demonstration of DNA laddering. Chymase induced SMC apoptosis in a dose- and time- dependent manner, and its proteolytic activity was essential for the proapoptotic effect. In addition to rat chymase, recombinant human chymase was also found to induce apoptosis of human coronary artery SMCs in culture. These results suggest that mast cells may participate in the apoptotic regulation of SMCs in atherosclerotic lesions.
Key Words: apoptosis • smooth muscle • atherosclerosis • mast cells • chymase
This article has been cited by other articles:
 |
|
 |
|
  T. Tsuruda, J. Kato, K. Hatakeyama, K. Kojima, M. Yano, Y. Yano, K. Nakamura, F. Nakamura-Uchiyama, Y. Matsushima, T. Imamura, et al. Adventitial Mast Cells Contribute to Pathogenesis in the Progression of Abdominal Aortic Aneurysm Circ. Res., June 6, 2008; 102(11): 1368 - 1377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Heikkila, S. Latti, M. J. Leskinen, J. K. Hakala, P. T. Kovanen, and K. A. Lindstedt Activated Mast Cells Induce Endothelial Cell Apoptosis by a Combined Action of Chymase and Tumor Necrosis Factor-{alpha} Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 309 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Fischer, S. Zheng, R. Fan, and J. A. Voynow Neutrophil elastase inhibition of cell cycle progression in airway epithelial cells in vitro is mediated by p27kip1 Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L762 - L768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Bot, S. C.A. de Jager, A. Zernecke, K. A. Lindstedt, T. J.C. van Berkel, C. Weber, and E. A.L. Biessen Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E-Deficient Mice Circulation, May 15, 2007; 115(19): 2516 - 2525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsuruda, J. Kato, K. Hatakeyama, A. Yamashita, K. Nakamura, T. Imamura, K. Kitamura, T. Onitsuka, Y. Asada, and T. Eto Adrenomedullin in mast cells of abdominal aortic aneurysm Cardiovasc Res, April 1, 2006; 70(1): 158 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, E. H. Herman, D. G. Robertson, M. D. Reily, A. Knapton, H. V. Ratajczak, N. Rifai, R. Honchel, K. T. Blanchard, R. E. Stoll, et al. Mechanisms and Biomarkers of Cardiovascular Injury Induced by Phosphodiesterase Inhibitor III SK&F 95654 in the Spontaneously Hypertensive Rat Toxicol Pathol, February 1, 2006; 34(2): 152 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Oltmanns, M. B. Sukkar, S. Xie, M. John, and K. F. Chung Induction of Human Airway Smooth Muscle Apoptosis by Neutrophils and Neutrophil Elastase Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 334 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Lindstedt, M. J. Leskinen, and P. T. Kovanen Proteolysis of the Pericellular Matrix: A Novel Element Determining Cell Survival and Death in the Pathogenesis of Plaque Erosion and Rupture Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1350 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Ho, R. E. Ruffin, C. Murgia, L. Li, S. A. Krilis, and P. D. Zalewski Labile Zinc and Zinc Transporter ZnT4 in Mast Cell Granules: Role in Regulation of Caspase Activation and NF-{kappa}B Translocation J. Immunol., June 15, 2004; 172(12): 7750 - 7760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O Ozdemir and S Savasan The role of mast cells in bone marrow diseases J. Clin. Pathol., January 1, 2004; 57(1): 108 - 109. [Full Text]
|
|
|
|
|
|
J. Ejiri, N. Inoue, T. Tsukube, T. Munezane, Y. Hino, S. Kobayashi, K.-i. Hirata, S. Kawashima, S. Imajoh-Ohmi, Y. Hayashi, et al. Oxidative stress in the pathogenesis of thoracic aortic aneurysm: Protective role of statin and angiotensin II type 1 receptor blocker Cardiovasc Res, October 1, 2003; 59(4): 988 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Cullen, R. Baetta, S. Bellosta, F. Bernini, G. Chinetti, A. Cignarella, A. von Eckardstein, A. Exley, M. Goddard, M. Hofker, et al. Rupture of the Atherosclerotic Plaque: Does a Good Animal Model Exist? Arterioscler. Thromb. Vasc. Biol., April 1, 2003; 23(4): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Leskinen, K. A. Lindstedt, Y. Wang, and P. T. Kovanen Mast Cell Chymase Induces Smooth Muscle Cell Apoptosis by a Mechanism Involving Fibronectin Degradation and Disruption of Focal Adhesions Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 238 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Martinet, D. M. Schrijvers, G. R.Y. De Meyer, J. Thielemans, M. W.M. Knaapen, A. G. Herman, and M. M. Kockx Gene Expression Profiling of Apoptosis-Related Genes in Human Atherosclerosis: Upregulation of Death-Associated Protein Kinase Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2023 - 2029. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Lazaar, M. I. Plotnick, U. Kucich, I. Crichton, S. Lotfi, S. K. P. Das, S. Kane, J. Rosenbloom, R. A. Panettieri Jr., N. M. Schechter, et al. Mast Cell Chymase Modifies Cell-Matrix Interactions and Inhibits Mitogen-Induced Proliferation of Human Airway Smooth Muscle Cells J. Immunol., July 15, 2002; 169(2): 1014 - 1020. [Abstract] [Full Text] [PDF]
|
|