title: [Vascular injury by glucocorticoid; involvement of apoptosis of endothelial cells].
abstract: Idiopathic osteonecrosis of the femoral head (IONF) is known to be caused by tissue ischemia, which is mainly associated with high-dose glucocorticoid (GC) used for the treatments of systemic autoimmune diseases. However, precise pathological mechanisms of IONF remain unclear. We first found that hypoxia-inducible factor (HIF) -1alpha, a major transcription factor rapidly induced under hypoxic conditions, was highly expressed on endothelial cells of femoral head in patients with IONF. Transfection of HIF-1alpha induced p21-mediated arrest of cell cycle and subsequent apoptosis in endothelial cells. High dose GC also induced cell cycle arrest and apoptosis. Furthermore, there were additional effects between HIF-1alpha and high dose GC for the growth arrests and apoptosis of the cells. However, C-type natriuretic peptide (CNP) inhibited both cell cycle arrest and apoptosis of the endothelial cells in a concentration-dependent manner. There results indicate that hypoxia and high-dose GC play a pivotal role for vascular injury and that CNP could have a potential to protect the vascular injury seen in patients with IONF.
authors.affiliation: University of Occupational and Environmental Health, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Okada
authors.forename: Takahisa
authors.initials: T
authors.lastname: Tanikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iida
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D017209:Apoptosis; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005270:Femur Head / Q000098:blood supply / Q000166:cytology*; D005271:Femur Head Necrosis / Q000209:etiology*; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007511:Ischemia; D020098:Natriuretic Peptide, C-Type / Q000502:physiology; D014162:Transfection
chemical_list: D005938:Glucocorticoids; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020098:Natriuretic Peptide, C-Type