Endothelium-derived microparticles inhibit angiogenesis in the heart and enhance the inhibitory effects of XXXX on angiogenesis.

@entity1 @entity754 @entity753 @entity1007 @entity19 @entity453
Therapeutic angiogenesis remains unsuccessful in @entity453 . It is known that plasma endothelium-derived microparticles (EMPs) are increased in @entity453 and that @entity1007 can inhibit angiogenesis. We evaluated the relationship between EMPs and @entity1007 in the impairment of angiogenesis. EMPs isolated from @entity1 umbilical vein endothelial cells were injected into @entity754 -null (LDLr(-/-)) @entity19 fed a Western diet for 2 wk and C57BL6 @entity19 for 6 h or were directly added to the tissue culture media. Hearts isolated from @entity19 were sectioned and cultured, and endothelial tube formation was measured. The expression and phosphorylation of endothelial NO synthase (eNOS) and the generation of NO in the hearts were determined. Angiogenesis was inhibited by pathophysiological concentrations of EMPs but not physiological concentrations of EMPs in hearts from C57BL6 @entity19 . However, angiogenesis was inhibited by EMPs at both physiological and pathophysiological concentrations of EMPs in hearts from @entity753 (-/-) @entity19 . Pathophysiological concentrations of EMPs decreased eNOS phosphorylation at Ser(1177) and NO generation without altering eNOS expression in hearts from C57BL6 @entity19 . Both physiological and pathophysiological concentrations of EMPs decreased not only eNOS phosphorylation at Ser(1177) and NO generation, but eNOS expression in @entity753 hearts from LDLr(-/-) @entity19 . These data demonstrated that pathophysiological concentrations of EMPs could inhibit angiogenesis in hearts by decreasing eNOS activity. EMPs and @entity1007 mutually enhanced their inhibitory effect of angiogenesis by inducing eNOS dysfunction. Our findings suggest a novel mechanism by which @entity1007 impairs angiogenesis.
