Extracellular XXXX metabolism and @entity730 in vascular smooth muscle.

@entity845 @entity35 @entity34179 @entity19 @entity10749 @entity34180 @entity730 @entity729 @entity9955 @entity855
Extracellular inorganic @entity9955 (ePP(i)) is an important endogenous inhibitor of @entity729 , but it is not known whether systemic or local vascular PP(i) metabolism controls @entity730 . To determine the role of ePP(i) in vascular smooth muscle, we identified the pathways responsible for ePP(i) production and hydrolysis in @entity35 and @entity19 aortas and manipulated them to demonstrate their role in the @entity730 of isolated aortas in culture. @entity35 and @entity19 aortas contained mRNA for ectonucleotide pyrophosphatase/phosphodiesterases ( @entity34179 -3), the putative PP(i) transporter @entity34180 , and @entity10749 ( @entity10749 ). Synthesis of PP(i) from @entity855 in aortas was blocked by b,y- @entity845 - @entity855 , an inhibitor of NPPs. Aortas from @entity19 lacking @entity34179 ( @entity34179 (-/-)) did not synthesize PP(i) from @entity855 and exhibited increased @entity730 in culture. Although @entity34180 -mediated transport of PP(i) could not be demonstrated in aortas, aortas from mutant ( @entity34180 / @entity34180 ) @entity19 calcified more in culture than did aortas from normal ( @entity34180 / @entity34180 ) @entity19 . Hydrolysis of PP(i) was reduced 25% by b,y- @entity845 - @entity855 and 50% by inhibition of @entity10749 . Hydrolysis of PP(i) was increased in cells overexpressing @entity10749 or NPP3 but not @entity34179 and was not reduced in @entity34179 (-/-) aortas. Overexpression of @entity10749 increased @entity730 of cultured aortas. The results show that smooth muscle @entity34179 and @entity10749 control @entity729 through effects on synthesis and hydrolysis of ePP(i), indicating an important inhibitory role of locally produced PP(i). Smooth muscle @entity34180 also affects @entity730 , but this may not be mediated through transport of PP(i). NPP3 is identified as an additional pyrophosphatase that could influence @entity729 .
