Lincoln T M, Dey N B, Boerth N J, Cornwell T L, Soff G A
Department of Pathology, University of Alabama at Birmingham 35294-0019, USA.
Acta Physiol Scand. 1998 Dec;164(4):507-15. doi: 10.1111/j.1365-201x.1998.tb10700.x.
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.
