An assessment of the role of the inhibitory gamma subunit of the retinal @entity8262 phosphodiesterase and its effect on the p42/ @entity10861 mitogen-activated protein kinase pathway in animal and cellular models of XXXX .

@entity1 @entity10861 @entity120 @entity8262 @entity519 @entity35
1. We have previously reported that the inhibitory gamma subunit of the rod photoreceptor type 6 @entity8262 phosphodiesterase (PDEgamma) is expressed in nonretinal tissues and is involved in the stimulation of the p42/ @entity10861 mitogen-activated protein kinase (MAPK) pathway by growth factors and G-protein-coupled receptor agonists. We have now investigated whether PDEgamma plays a role in modulating chronic @entity519 -dependent mitogenic signalling pathways in pulmonary smooth muscle from @entity35 with @entity120 ( @entity120 ). 2. We show for the first time that PDEgamma is expressed in @entity35 main, first, intrapulmonary and resistance pulmonary arteries. Moreover, its expression is increased in all the arteries to varying extents by chronic @entity519 . The extent of the increased expression of PDEgamma is correlated with an enhanced activation of p42/ @entity10861 in these vessels. 3. We also report that PDEgamma translation from mRNA transcript is increased in cultured @entity1 pulmonary artery smooth muscle cells subjected to chronic @entity519 for 14 days. This was correlated with @entity519 -dependent increase in p42/ @entity10861 MAPK activation. 4. In conclusion, our studies identify for the first time a major chronic @entity519 -dependent change in the phenotypic expression of an intermediate protein regulating mitogenic signalling in pulmonary arteries. This may have a significant effect on arterial remodelling in @entity120 . Future studies will focus on strategies designed to knockout rod PDEgamma to assess whether this rescues @entity35 from chronic @entity519 -dependent changes in arterial remodelling and @entity120 .
