COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury.
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.
Kim
Duk Hoon
DH
Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Korea.
Jung
Yu Jin
YJ
Lee
Ae Sin
AS
Lee
Sik
S
Kang
Kyung Pyo
KP
Lee
Tae Hwan
TH
Lee
Sang Yong
SY
Jang
Kyu Yun
KY
Moon
Woo Sung
WS
Choi
Kyu-Sil
KS
Yoon
Kwon-Ha
KH
Sung
Mi Jeong
MJ
Park
Sung Kwang
SK
Kim
Won
W
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*
C515576:COMP-Ang1 fusion protein; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins