© 2000 American Heart Association, Inc.
Vascular Biology |
Cyclic GMP–Dependent Protein Kinase Expression in Coronary Arterial Smooth Muscle in Response to Balloon Catheter Injury
From the Departments of Pathology (P.G.A., N.J.B., T.L.C., T.M.L.) and Medicine (M.L.), School of Medicine, University of Alabama at Birmingham, and the Department of Pharmacology (D.B.M.), School of Medicine, Tulane University, New Orleans, La.
Correspondence to Thomas M. Lincoln, PhD, Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL 35294-0019. E-mail lincoln{at}uab.edu
Abstract—Arterial smooth muscle cells undergo phenotypic and proliferative changes in response to balloon catheter injury. Nitric oxide (NO) and cGMP have been implicated in the inhibition of vascular smooth muscle cell proliferation and phenotypic modulation in cultured-cell studies. We have examined the expression of the major cGMP receptor protein in smooth muscle, cGMP-dependent protein kinase I (PKG), in response to balloon catheter injury in the swine coronary artery. On injury, there was a transient decrease in the expression of PKG in neointimal smooth muscle cells when compared with medial smooth muscle cells. The decrease in PKG expression was observed in the population of proliferating cells expressing the extracellular matrix protein osteopontin but not in cells present in the uninjured portion of the media. Coincident with the suppression of PKG expression in neointimal cells after injury, there was a marked increase in the expression of type II NO synthase (inducible NOS [iNOS], NOS-II) in the neointimal cells. These results suggest that PKG expression is transiently reduced in response to injury in the population of coronary arterial smooth muscle cells that are actively proliferating and producing extracellular matrix proteins. The reduction in PKG expression is also correlated temporally with increases in inflammatory activity in the injured vessels as assessed by iNOS expression. Coupled with our current knowledge regarding the role of PKG in the regulation of cultured cell phenotypes, these results imply that PKG may also regulate phenotypic modulation of vascular smooth muscle cells in vivo as well.
Key Words: nitric oxide • restenosis • cGMP • vascular smooth muscle • phenotype
This article has been cited by other articles:
 |
|
 |
|
  P. Weinmeister, R. Lukowski, S. Linder, C. Traidl-Hoffmann, L. Hengst, F. Hofmann, and R. Feil Cyclic Guanosine Monophosphate-dependent Protein Kinase I Promotes Adhesion of Primary Vascular Smooth Muscle Cells Mol. Biol. Cell, October 1, 2008; 19(10): 4434 - 4441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schleicher and W. C. Sessa Are the Mechanisms for NO-Dependent Vascular Remodeling Different From Vasorelaxation In Vivo? Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1207 - 1208. [Full Text] [PDF]
|
|
|
|
|
|
R. Lukowski, P. Weinmeister, D. Bernhard, S. Feil, M. Gotthardt, J. Herz, S. Massberg, A. Zernecke, C. Weber, F. Hofmann, et al. Role of Smooth Muscle cGMP/cGKI Signaling in Murine Vascular Restenosis Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1244 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Zhang, S. Zhuang, D. E. Casteel, D. J. Looney, G. R. Boss, and R. B. Pilz A Cysteine-rich LIM-only Protein Mediates Regulation of Smooth Muscle-specific Gene Expression by cGMP-dependent Protein Kinase J. Biol. Chem., November 16, 2007; 282(46): 33367 - 33380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhou, C. Dasgupta, S. Negash, and J. U. Raj Modulation of pulmonary vascular smooth muscle cell phenotype in hypoxia: role of cGMP-dependent protein kinase Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1459 - L1466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W.Y. Chung, P. Rauniyar, H. Luo, Y. N. Hsiang, C. van Breemen, and E. B. Okon Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and nitric oxide production J. Thorac. Cardiovasc. Surg., October 1, 2006; 132(4): 925 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. I. Levy and S. Chaturvedi Perforator stroke following intracranial stenting: A sacrifice for the greater good? Neurology, June 27, 2006; 66(12): 1803 - 1804. [Full Text] [PDF]
|
|
|
|
|
|
Y. Zeng, S. Zhuang, J. Gloddek, C.-C. Tseng, G. R. Boss, and R. B. Pilz Regulation of cGMP-dependent Protein Kinase Expression by Rho and Kruppel-like Transcription Factor-4 J. Biol. Chem., June 23, 2006; 281(25): 16951 - 16961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Tilley and D. H. Maurice Vascular Smooth Muscle Cell Phenotype-Dependent Phosphodiesterase 4D Short Form Expression: Role of Differential Histone Acetylation on cAMP-Regulated Function Mol. Pharmacol., September 1, 2005; 68(3): 596 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sellak, C. Choi, N. Browner, and T. M. Lincoln Upstream Stimulatory Factors (USF-1/USF-2) Regulate Human cGMP-dependent Protein Kinase I Gene Expression in Vascular Smooth Muscle Cells J. Biol. Chem., May 6, 2005; 280(18): 18425 - 18433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Browner, N. B. Dey, K. D. Bloch, and T. M. Lincoln Regulation of cGMP-dependent Protein Kinase Expression by Soluble Guanylyl Cyclase in Vascular Smooth Muscle Cells J. Biol. Chem., November 5, 2004; 279(45): 46631 - 46636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Browner, H. Sellak, and T. M. Lincoln Downregulation of cGMP-dependent protein kinase expression by inflammatory cytokines in vascular smooth muscle cells Am J Physiol Cell Physiol, July 1, 2004; 287(1): C88 - C96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Pilz and D. E. Casteel Regulation of Gene Expression by Cyclic GMP Circ. Res., November 28, 2003; 93(11): 1034 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Feil, S. M. Lohmann, H. de Jonge, U. Walter, and F. Hofmann Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System: Insights From Genetically Modified Mice Circ. Res., November 14, 2003; 93(10): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sinnaeve, J.-D. Chiche, H. Gillijns, N. Van Pelt, D. Wirthlin, F. Van de Werf, D. Collen, K. D. Bloch, and S. Janssens Overexpression of a Constitutively Active Protein Kinase G Mutant Reduces Neointima Formation and In-Stent Restenosis Circulation, June 18, 2002; 105(24): 2911 - 2916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Dunkerley, D. G. Tilley, D. Palmer, H. Liu, S. L. Jimmo, and D. H. Maurice Reduced Phosphodiesterase 3 Activity and Phosphodiesterase 3A Level in Synthetic Vascular Smooth Muscle Cells: Implications for Use of Phosphodiesterase 3 Inhibitors in Cardiovascular Tissues Mol. Pharmacol., May 1, 2002; 61(5): 1033 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sellak, X. Yang, X. Cao, T. Cornwell, G. A. Soff, and T. Lincoln Sp1 Transcription Factor as a Molecular Target for Nitric Oxide- and Cyclic Nucleotide-Mediated Suppression of cGMP-Dependent Protein Kinase-I{alpha} Expression in Vascular Smooth Muscle Cells Circ. Res., March 8, 2002; 90(4): 405 - 412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Lincoln, N. Dey, and H. Sellak Signal Transduction in Smooth Muscle: Invited Review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression J Appl Physiol, September 1, 2001; 91(3): 1421 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sellak, X. Yang, X. Cao, T. Cornwell, G. A. Soff, and T. Lincoln Sp1 Transcription Factor as a Molecular Target for Nitric Oxide- and Cyclic Nucleotide-Mediated Suppression of cGMP-Dependent Protein Kinase-I{alpha} Expression in Vascular Smooth Muscle Cells Circ. Res., March 8, 2002; 90(4): 405 - 412. [Abstract] [Full Text] [PDF]
|
|