The roles of NF-κB pathway in the endothelium

点击翻译按钮获取中文摘要

We generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased, while blood flow and mitochondrial contents in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged lifespan. These anti-aging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity.