cGMP-dependent protein kinase expression restores contractile function in cultured vascular smooth muscle cells.

Brophy CM, Woodrum DA, Pollock J, Dickinson M, Komalavilas P, Cornwell TL, Lincoln TM
J Vasc Res. 2002 39 (2): 95-103

PMID: 12011581 · DOI:10.1159/000057758

Vascular diseases, such as atherosclerosis and restenosis following angioplasty or transplantation, are due to abnormal vascular smooth muscle growth and gene expression. The smooth muscle cells (SMC) in response to injury lose their contractile function, become highly proliferative and synthesize and secrete extracellular matrix proteins. Similar changes in the phenotypic properties of vascular SMC occur during in vitro culture. In this report, we examined whether restoration of the expression of the major receptor protein for nitric oxide (NO) signaling in smooth muscle, the guanosine 3':5' cyclic monophosphate (cGMP)-dependent protein kinase (PKG), reestablished contractile function to cultured rat aortic SMC. Contractile function was monitored using the silicone polymer wrinkle assay used previously to determine contractility in cultured mesangial cells. Noncontractile rat aortic smooth muscle cells transfected with the cDNA encoding the type I isoform of PKG, but not those transfected with empty vector, formed discreet wrinkles on the substratum in response to serum indicative of contraction. Treatment of the PKG-expressing SMC with sodium nitroprusside (SNP), an NO donor, and with cGMP analogs, or with the adenylyl cyclase activator, forskolin, and with adenosine 3':5' cyclic monophosphate (cAMP) analogs reduced wrinkling. The expression of a major PKG substrate protein involved in smooth muscle relaxation, heat shock-related protein-20 (HSP20), was also reestablished in PKG-expressing SMC. Treatment of the PKG-expressing SMC with nitroprusside resulted in phosphorylation of HSP20. Collectively, these results indicate that PKG expression is important to establish contractility to SMC in culture.

Copyright 2002 S. Karger AG, Basel

MeSH Terms (24)

Animals Aorta, Abdominal Aorta, Thoracic Bucladesine Cells, Cultured Colforsin Cyclic AMP Cyclic GMP-Dependent Protein Kinases Gene Expression Heat-Shock Proteins HSP20 Heat-Shock Proteins Isoenzymes Muscle, Smooth, Vascular Muscle Contraction Nitric Oxide Nitric Oxide Donors Nitroprusside Phosphoproteins Phosphorylation Rats Rats, Sprague-Dawley Signal Transduction Thionucleotides Transfection

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