Deletion of the alternatively spliced fibronectin EIIIA domain in XXXX reduces @entity731 .

@entity6970 @entity455 @entity19 @entity731 @entity165
The alternatively spliced and highly conserved EIIIA domain of fibronectin (FN) is included in most FN of the extracellular matrix in embryos. In adults, both extracellular matrix and plasma FN essentially lack EIIIA. In diverse inflammatory situations however, EIIIA is specifically included by regulated RNA splicing. In @entity731 , FN, including the EIIIA domain (EIIIA-FN), is abundant, whereas FN in the flanking vessel wall lacks EIIIA. Lesional EIIIA-FN is localized with endothelial cells and macrophage foam cells. To directly test the function of EIIIA-FN, we generated EIIIA-null (EIIIA(-/-)) @entity19 that lack the EIIIA exon and crossed them with @entity6970 ( @entity6970 )-null ( @entity6970 (-/-)) @entity19 that develop @entity455 . Compared with @entity6970 (-/-) controls, EIIIA(-/-) @entity6970 (-/-) @entity19 had significantly smaller lesions throughout the aortic tree. EIIIA-FN was increased in @entity6970 (-/-) plasma, and total plasma @entity165 was reduced in EIIIA(-/-) @entity6970 (-/-) @entity19 , specifically in large lipoprotein particles, suggesting a functional role for plasma EIIIA-FN. To assess a role for macrophage EIIIA-FN in the vessel wall, we conducted in vitro foam cell assays. EIIIA(-/-) @entity6970 (-/-) macrophages accumulated significantly less intracellular lipid than control @entity6970 (-/-) cells. These results provide genetic evidence that suggests roles for EIIIA-FN in plasma lipoprotein metabolism and in foam cell formation.
