Roles Of Nuclear Factor-κB In Apoptosis Of Endothelial Cells

Objectives: The mortality and morbidity of cardiovascular disease is increasing, so more studies is to clear the pathogenesis of cardiovascular disease. It is known that the endothelial cells (EC), which line the lumen of the blood vessels, are not passive bystanders but are active responders to stimuli like activated leukocytes and cytokines. The dysfunction of EC can provoke the progression of cardiovascular disease. In cells, NF-κB, a dimeric transcription factor, is retained in the cytoplasm but enters the nucleus in response to various stimuli. The activation of NF-κB requires sequential phosphorylation, ubiquitination, and degradation of IκB. Activation of NF-κB can result in biological effects, such as apoptosis, proliferation, etc. Angiotensin II (AngII), as the main active peptide of the RAS, regulates both cellular and physiological responses in the cardiovascular system. However, AngII is also implicated in pathophysiological processes associated with vascular injury and repair. It promotes generation of oxidative stress in the vascular wall, which appears to be a key mediator of AngII-induced endothelial dysfunction. Meanwhile, TNF-αis also an important cytokine, which cause the apoptosis of cells. As a result, the purpose of the present study is to elucidate the role of NF-κB in the apoptosis of EC induced by AngII and TNF-α.Methods: (1) The EC was treated with AngII alone. The apoptosis rates were measured by Tunel. The activity of NF-κB was assessed using EMSA. In addition, AT1 and AT2 were evaluated for their influence on the activity of NF-κB and apoptosis of EC induced by AngII. The role of NF-κB in apoptosis of EC induced by AngII was evaluated.(2) After EC was induced with AngII, the protein and gene expression of inducible nitric oxide syntheses were measured with Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), and the content of NO was also observed.(3) After EC was induced with TNF-α, the apoptosis rate was measured using Tunel and DNA Ladder and the activity of NF-κB was assessed by EMSA. The role of NF-κB in...