Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype.
Nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) have been reported to prevent vascular smooth muscle cell (VSMC) proliferation and have beneficial effects to reduce intimal thickening in response to arterial injury. The purpose of this study was to determine whether the downstream effector molecule of NO-cGMP signaling, cyclic GMP-dependent protein kinase (PKG), regulates phenotypic modulation and proliferation in cultured rat aortic VSMC. PKG-expressing VSMC lines were created by transfection of PKG-deficient cell lines and characterized. All forms of PKG, i.e. PKG-I alpha and PKG-I beta, as well as the constitutively active catalytic domain of PKG-I, transformed dedifferentiated 'synthetic' VSMC to a more contractile-like morphology. PKG expression resulted in an increased production of the contractile phenotype marker proteins, smooth muscle myosin heavy chain-2, calponin and alpha-actin and restored the capacity of cAMP and cGMP analogues to inhibit platelet-derived growth factor (PDGF)-induced cell migration. On the other hand, PKG expression had no significant effects on PDGF-induced cell proliferation. These results suggest that PKG expression contributes to the regulation of a contractile-like phenotypic expression in cultured VSMC, and the suppression of PKG expression during cultured growth in vitro may permit the modulation of cells to a more synthetic, dedifferentiated phenotype.
Boerth
N J
NJ
Department of Pathology, University of Alabama at Birmingham, 35294-0019, USA.
Dey
N B
NB
Cornwell
T L
TL
Lincoln
T M
TM
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D005576:Colforsin; D017869:Cyclic GMP-Dependent Protein Kinases; D018995:Myosin Heavy Chains