Nitric oxide--cyclic GMP pathway regulates vascular smooth muscle cell phenotypic modulation: implications in vascular diseases.
The role of cGMP-dependent protein kinase (PKG) in the regulation of rat aortic vascular smooth muscle cells (VSMC) phenotype was examined using a transfected cell culture system. Repetitively passaged VSMC do not express PKG and exist in the synthetic phenotype. Transfection of PKG-l alpha cDNA, or the active catalytic domain of PKG-l alpha, resulted in the appearance of VSMC having a morphology consistent with the contractile phenotype. PKG-expressing cells also contained markers for the contractile phenotype (for example, smooth muscle specific myosin heavy chain, calponin, alpha-actin) and reduced levels of synthetic phenotype markers (osteopontin, thrombospondin). PKG-transfected VSMC have also reduced the levels of fibroblast growth factor receptors 1 and 2, consistent with the establishment of a more contractile phenotype. The regulation of PKG expression in VSMC is largely undefined; however, continuous exposure of cultured bovine aortic smooth muscle cells with nitric oxide (NO)-donor drugs or cyclic nucleotide analogues reduced the expression of PKG. These results suggest that PKG occupies a critical role in VSMC phenotype and that suppression of PKG expression during inflammation or injury promotes a more synthetic state of the VSMC.
Lincoln
T M
TM
Department of Pathology, University of Alabama at Birmingham 35294-0019, USA.
Dey
N B
NB
Boerth
N J
NJ
Cornwell
T L
TL
Soff
G A
GA
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D008858:Microscopy, Phase-Contrast; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection / Q000502:physiology; D014652:Vascular Diseases / Q000503:physiopathology*
D009569:Nitric Oxide; D000242:Cyclic AMP