Smooth muscle--specific expression of XXXX induces endothelial sprouting in renal arterial microvessels.

@entity1426 @entity15759 @entity27146 @entity48194 @entity70963 @entity27057 @entity33374
@entity48194 has been characterized as the most efficient @entity1426 omega-hydroxylase catalyzing the formation of @entity15759 ( @entity15759 ), a potent constrictor of the renal and cerebral microcirculation and a mitogen for smooth muscle cells. We constructed adenoviruses expressing the @entity48194 cDNA or LacZ under the control of the smooth muscle cell-specific promoter @entity27057 (Ad-SM22-4A1 and Ad-SM22-nLacZ, respectively). Beta-galactosidase expression was detected in Ad-SM22-nLacZ-transduced vascular smooth muscle A7r5 and PAC1 cells, but not in Ad-SM22-nLacZ-transduced 3T3 fibroblasts or vascular endothelial cells. Likewise, @entity48194 mRNA and protein were detected in Ad-SM22-4A1-transduced A7r5 and PAC1 cells. Ad-SM22-4A1-transduced A7r5 cells metabolized @entity27146 to @entity70963 at a rate 5 times greater than that of cells transduced with Ad-SM22-nLacZ (4.79+/-1.77 versus 0.97+/-0.57 nmol @entity70963 /10(6) cells per h). Smooth muscle-specific LacZ expression was also detected in microdissected renal interlobar arteries transduced with Ad-SM22-nLacZ. Arteries transduced with Ad-SM22-4A1 produced higher levels of @entity15759 (4.04+/-0.29 and 13.43+/-2.84 ng/mg protein in Ad-SM22-nLacZ-transduced and Ad-SM22-4A1-transduced arteries, respectively) and demonstrated a marked angiogenic activity measured as the total length of sprouting neovessels (12.63+/-3.66 mm in Ad-SM22-4A1-transduced vessels versus 1.79+/-0.89 mm in Ad-SM22-nLacZ-transduced vessels). This angiogenic activity represented endothelial cell sprouting and was fully blocked by treatment with @entity33374 , a selective inhibitor of CYP4A-catalyzed reactions. The inhibitory effect of @entity33374 was reversed by addition of a @entity15759 agonist. We conclude that Ad-SM22-4A1 drives a smooth muscle-specific functional expression of @entity48194 and demonstrates increased angiogenesis, presumably via increased production of @entity15759 .
