© 1996 American Heart Association, Inc.
Articles |
Nitric Oxide Reversibly Inhibits the Migration of Cultured Vascular Smooth Muscle Cells
From the Departments of Physiology (R.S., R.C.W.), Surgery (R.S., E.G.M., J.C.S.), and Pathology (D.G.), University of Michigan Medical School, Ann Arbor.
Correspondence to Rajabrata Sarkar, MD, PhD, Department of Physiology, University of Michigan Medical School, 7813 MS II, 1301 Catherine Rd, Ann Arbor, MI 48109-0622. E-mail rsarkar@ucla.edu.
Abstract Augmentation of nitric oxide (NO) production in vivo decreases lesions in a variety of models of arterial injury, and inhibition of NO synthase exacerbates experimental intimal lesions. Both vascular smooth muscle cell (VSMC) proliferation and migration contribute to lesion formation. Although NO inhibits VSMC proliferation, its effects on VSMC migration are unknown. To test the hypothesis that NO inhibits VSMC migration independent of inhibition of proliferation, we examined migration of rat aortic VSMCs after wounding of a confluent culture in the presence of chemical donors of NO. Hydroxyurea was used to eliminate any confounding effect of NO on proliferation. Three NO donors, diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited concentration-dependent inhibition of both number of migrating VSMCs and maximal distance migrated. Inhibition of migration was also seen with 8-Br-cGMP, suggesting that activation of guanylate cyclase may play a role in mediating the antimigratory effects of NO. Migration resumed after removal of NO donors, as evidenced by an increase in distance migrated. Measurement of VSMC protein synthesis and mitochondrial respiration indicated that inhibition of migration by NO donors was not due to metabolic cytostasis. These findings indicate that NO reversibly inhibits VSMC migration independent of proliferation or cytotoxicity, a novel mechanism by which both endogenous and pharmacological NO may alter vascular pathology.
Key Words: atherosclerosis • cell migration • nitric oxide
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V. Poppa, J. K. Miyashiro, M. A. Corson, and B. C. Berk Endothelial NO Synthase Is Increased in Regenerating Endothelium After Denuding Injury of the Rat Aorta Arterioscler Thromb Vasc Biol, August 1, 1998; 18(8): 1312 - 1321. [Abstract] [Full Text] [PDF]
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K. M. Channon, H. Qian, S. A. Youngblood, E. Olmez, G. A. Shetty, V. Neplioueva, M. A. Blazing, and S. E. George Acute Host-Mediated Endothelial Injury After Adenoviral Gene Transfer in Normal Rabbit Arteries : Impact on Transgene Expression and Endothelial Function Circ. Res., June 29, 1998; 82(12): 1253 - 1262. [Abstract] [Full Text] [PDF]
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M. Yamamoto, M. Aoyagi, N. Fukai, Y. Matsushima, and K. Yamamoto Differences in Cellular Responses to Mitogens in Arterial Smooth Muscle Cells Derived From Patients With Moyamoya Disease Stroke, June 1, 1998; 29(6): 1188 - 1193. [Abstract] [Full Text] [PDF]
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J o. Koglin, T. Glysing-Jensen, J. S. Mudgett, and M. E. Russell Exacerbated Transplant Arteriosclerosis in Inducible Nitric Oxide–Deficient Mice Circulation, May 26, 1998; 97(20): 2059 - 2065. [Abstract] [Full Text] [PDF]
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L. Chen, G. Daum, R. Forough, M. Clowes, U. Walter, and A. W. Clowes Overexpression of Human Endothelial Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells and in Balloon-Injured Carotid Artery Circ. Res., May 4, 1998; 82(8): 862 - 870. [Abstract] [Full Text] [PDF]
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P. R. Myers and M. A. Tanner Vascular Endothelial Cell Regulation of Extracellular Matrix Collagen : Role of Nitric Oxide Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 717 - 722. [Abstract] [Full Text] [PDF]
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N. B. Dey, N. J. Boerth, J. E. Murphy-Ullrich, P.-L. Chang, C. W. Prince, and T. M. Lincoln Cyclic GMP–Dependent Protein Kinase Inhibits Osteopontin and Thrombospondin Production in Rat Aortic Smooth Muscle Cells Circ. Res., February 9, 1998; 82(2): 139 - 146. [Abstract] [Full Text] [PDF]
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I. J. Kullo, R. S. Schwartz, V. J. Pompili, M. Tsutsui, S. Milstien, L. A. Fitzpatrick, Z. S. Katusic, and T. O'Brien Expression and Function of Recombinant Endothelial NO Synthase in Coronary Artery Smooth Muscle Cells Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2405 - 2412. [Abstract] [Full Text]
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J.-L. Balligand and P. J. Cannon Nitric Oxide Synthases and Cardiac Muscle : Autocrine and Paracrine Influences Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1846 - 1858. [Abstract] [Full Text]
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W. Aji, S. Ravalli, M. Szabolcs, X.-c. Jiang, R. R. Sciacca, R. E. Michler, and P. J. Cannon L-Arginine Prevents Xanthoma Development and Inhibits Atherosclerosis in LDL Receptor Knockout Mice Circulation, January 21, 1997; 95(2): 430 - 437. [Abstract] [Full Text]
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Y. Ryu, N. Takuwa, N. Sugimoto, S. Sakurada, S. Usui, H. Okamoto, O. Matsui, and Y. Takuwa Sphingosine-1-Phosphate, a Platelet-Derived Lysophospholipid Mediator, Negatively Regulates Cellular Rac Activity and Cell Migration in Vascular Smooth Muscle Cells Circ. Res., February 22, 2002; 90(3): 325 - 332. [Abstract] [Full Text] [PDF]
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