OBJECTIVE: We evaluated whether @entity4357 3-kinase gamma ( @entity48971 ) plays a role in reparative @entity2295 and endothelial progenitor cell (EPC) function. METHODS AND RESULTS: Unilateral limb @entity63 was induced in @entity19 lacking the @entity48971 gene ( @entity48971 or expressing a catalytically inactive mutant ( @entity48971 ( @entity573 / @entity573 )) and @entity23 ( @entity23 ). Capillarization and arteriogenesis were reduced in @entity48971 -/- ischemic muscles resulting in delayed reperfusion compared with @entity23 , whereas reparative @entity2295 was preserved in @entity48971 ( @entity573 / @entity573 ). In @entity48971 -/- muscles, endothelial cell proliferation was reduced, apoptosis was increased, and interstitial space was infiltrated with leukocytes but lacked cKit+ progenitor cells that in @entity23 muscles typically surrounded arterioles. @entity48971 is constitutively expressed by @entity23 EPCs, with expression levels being upregulated by @entity519 . @entity48971 -/- EPCs showed a defect in proliferation, survival, integration into endothelial networks, and migration toward @entity19149 . The dysfunctional phenotype was associated with nuclear constraining of @entity34472 , reduced Akt and eNOS phosphorylation, and decreased @entity842 (NO) production. Pretreatment with an NO donor corrected the migratory defect of @entity48971 -/- EPCs. @entity48971 ( @entity573 / @entity573 ) EPCs showed reduced Akt phosphorylation, but constitutive activation of eNOS and preserved proliferation, survival, and migration. CONCLUSIONS: We newly demonstrated that @entity48971 modulates angiogenesis, arteriogenesis, and vasculogenesis by mechanisms independent from its kinase activity.

Phosphoinositide 3-kinase gamma gene knockout impairs postischemic XXXX and endothelial progenitor cell functions.

@entity34472 :: ('56458(Tax:10090)', 'Gene') :: ['FOXO1'] @entity573 :: ('MESH:C537014', 'Disease') :: ['KD'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2295 :: ('MESH:D015861', 'Disease') :: ['neovascularization'] @entity23 :: ('MESH:D007174', 'Disease') :: ['wild-type controls', 'WT'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity19149 :: ('20315(Tax:10090)', 'Gene') :: ['SDF-1'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity48971 :: ('30955(Tax:10090)', 'Gene') :: ['PI3Kgamma', 'PI3Kgamma-/-)'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol']
@entity2295 :: (MESH:D015861,Disease) :: ['neovascularization']
