title: COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury.
abstract: During sepsis endothelial dysfunction is an important pathogenetic mechanism in acute kidney injury (AKI). Lipopolysaccharide (LPS)-induced endotoxemia is associated with renal hemodynamic changes such as alterations of renal blood flow (RBF), vascular resistance, and glomerular filtration rate. We used adenoviral delivery of an engineered variant of native angiopoietin-1 (COMP-angiopoietin-1) containing anti-inflammatory and anti-permeability functions, to determine if regulation of renal endothelial cell dysfunction may have a beneficial role in preventing AKI during LPS-induced endotoxemia in mice. This treatment prevented the endotoxin-induced decrease of RBF and mean arterial pressure while improving glomerular filtration rate. Treatment also mitigated the effects of LPS on renal intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 protein expression, the number of ER-HR3-positive macrophages that infiltrated the kidney, serum nitrate/nitrite levels, renal inducible nitric oxide synthase protein expression, the induction of tubular epithelial reactive oxygen and nitrogen species, and renal microvascular permeability. Our findings show that COMP-angiopoietin-1, an endothelium-oriented therapeutic agent, protects against AKI caused by endotoxemia.
authors.affiliation: Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Lee
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Moon
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C515576:COMP-Ang1 fusion protein; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins