Pathophysiological response to hypoxia - From the molecular mechanisms of malady to drug discovery: Inflammatory responses of hypoxia-inducible factor 1α (HIF-1α) in T cells observed in development of vascular remodeling

Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. a major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (hif-1). impairment of hif-1- dependent inflammatory responses in t cells causes an augmented vascular remodeling induced by arterial injury,which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking hif-1α specifically in t cells. studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated t cells and augmented antibody production in response to a t-dependent antigen in the mutant mice. this minireview shows that hif-1α in t cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the t cell-mediated immune response and suggests potential new therapeutic strategies that target hif-1α. © the japanese pharmacological society.