title: Quiescent interplay between inducible nitric oxide synthase and tumor necrosis factor-alpha: influence on transplant graft vasculopathy in renal allograft dysfunction.
abstract: A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-alpha in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-alpha. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-alpha in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-alpha interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-alpha as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.
authors.affiliation: Department of Cardiothoracic Surgery, Faculty of Medicine and Surgery, PIC, Lahore, Pakistan.
authors.forename: Maqsood M
authors.initials: MM
authors.lastname: Elahi
authors.forename: Bashir M
authors.initials: BM
authors.lastname: Matata
authors.forename: Nadey S
authors.initials: NS
authors.lastname: Hakim
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D006084:Graft Rejection / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014652:Vascular Diseases / Q000201:enzymology / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II