Figure 1. Role of endothelial dysfunction and endothelial cell activation in vascular disease.

Cardiovascular risk factors, such as hypercholesterolemia, smoking, and oxidative stress, are important mediators of endothelial dysfunction, while proinflammatory cytokines, turbulent flow, and advanced glycation end-products (AGEs) are important mediators of endothelial cell activation via the activation of the transcription factor, NF-κB. NO from eNOS or NO donors reduces endothelial cell activation through inhibition of NF-κB. Loss of NO leads to increased endothelial cell activation. Likewise, endothelial cell activation can cause endothelial dysfunction. Both endothelial dysfunction and endothelial cell activation lead to atherosclerosis and vascular disease by increasing vasoconstriction, SMC proliferation, platelet aggregation, leukocyte adhesion, LDL oxidation, and MMP activation.