Role of NFκB in age-related vascular endothelial dysfunction in humans

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the United States and other industrialized societies.Older age is the major risk factor for development of CVD [1].Emerging evidence over the past 20 years suggests that the arterial vascular endothelium plays a critical role in the development of CVD, most notably, atherosclerosis.A healthy vascular endothelium is characterized by a tightly regulated balance of pro-and anti-oxidants, vasodilators and vasoconstrictors, and pro-and anti-inflammatory molecules.A diseased or dysfunctional endothelium displays a "pro-atherogenic" phenotype, losing its tightly regulated balance and adopting a prooxidant/vasoconstrictor/pro-inflammatory phenotype.A hallmark of arterial endothelial dysfunction is impaired endothelial dependent dilation, which is predictive of future CVD events [1,2].Aging leads to impaired endothelial dependent dilation associated elevated oxidative stress and a proinflammatory endothelial cell phenotype.Recent studies in humans by our group and by others in rodents suggest a critical role of nuclear factor κB (NFκB) in the pro-inflammatory / pro-oxidant linked suppression of endothelial dependent dilation with advancing aging [3][4][5][6][7].This perspective will discuss new information concerning the role of increased NFκB signaling in mediating vascular endothelial dysfunction with aging in humans.