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Endothelium Under Stress: Local and Systemic Messages

  • Sergey V. Brodsky
    Correspondence
    Address reprint requests to Michael S. Goligorsky, MD, PhD, Alvin I. Goodman Chair in Nephrology, Professor of Medicine, Pharmacology and Physiology Academic Chief, Division of Nephrology Director, Renal Research Institute New York Medical College, 15 Dana Rd, Basic Sci Bldg, r. C-23, Valhalla, NY 10595
    Affiliations
    Department of Pathology, The Ohio State University, Columbus, OH
    Search for articles by this author
  • Michael S. Goligorsky
    Affiliations
    Department of Medicine, Department of Pharmacology, and Department of Physiology, Renal Research Institute, New York Medical College, Valhalla, NY
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      Summary

      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.

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