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 ao rtic vascular smooth muscle cells (VSMC) phenotype was examined using a tra nsfected cell culture system. Repetitively passaged VSMC do not express PKG and exist in the synthetic phenotype. Transfection of PKG-1 alpha cDNA, or the active catalytic domain of rKG-1 alpha, resulted in the appearance of VSMC having a morphology consistent with the contractile phenotype. PKG-exp ressing cells also contained markers for the contractile phenotype (for exa mple, 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 f actor receptors 1 and 2, consistent with the establishment of a more contra ctile phenotype. The regulation of PKG expression in VSMC is largely undefi ned; however, continuous exposure of cultured bovine aortic smooth muscle c ells with nitric oxide (NO)-donor drugs or cyclic nucleotide analogues redu ced the expression of PKG. These results suggest that PKG occupies a critic al role in VSMC phenotype and that suppression of PKG expression during inf lammation or injury promotes a more synthetic state of the VSMC.