Endothelium Under Stress: Local and Systemic Messages

Endothelial responses to stressors are nonuniform and follow the rules of stress-induced hormesis. Responses to the same stressor, depending on its intensity, can range from pro-regenerative to pro-lethal. Exposure to sublethal stressors induces a programmed response that results in stress resistance, whereas a lethal level of a stressor accelerates cell demise. Diverse stressors turn on several default programs within the cells; such programs tend to induce anti-oxidative defenses and anti-inflammatory and pro-survival systems, whereas others tend to switch on pro-apoptotic systems. The response of the kidney endothelium to various forms of acute kidney injury follows these general principles. It is characterized by a proinflammatory pattern that includes up-regulation of different adhesion molecules promoting endothelial-leukocyte interactions, generation of reactive oxygen species, with formation of oxidative and nitrosative stress and mitochondrial damage. Simultaneously, a series of adaptive mechanisms, both local and systemic, are ignited. Stressed endothelial cells broadcast distress signals systemically; these signals can be directed toward the restoration of homeostasis or aggravation of the original insult.