Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities

Rinrada Kietadisorn, Rio P. Juni, An L. Moens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

139 Citations (Web of Science)

Abstract

Kietadisorn R, Juni RP, Moens AL. Tackling endothelial dysfunction by modulating NOS uncoupling: new insights into its pathogenesis and therapeutic possibilities. Am J Physiol Endocrinol Metab 302: E481-E495, 2012. First published December 13, 2011; doi:10.1152/ajpendo.00540.2011.-Endothelial nitric oxide synthase (eNOS) serves as a critical enzyme in maintaining vascular pressure by producing nitric oxide (NO); hence, it has a crucial role in the regulation of endothelial function. The bioavailability of eNOS-derived NO is crucial for this function and might be affected at multiple levels. Uncoupling of eNOS, with subsequently less NO and more superoxide generation, is one of the major underlying causes of endothelial dysfunction found in atherosclerosis, diabetes, hypertension, cigarette smoking, hyperhomocysteinemia, and ischemia/reperfusion injury. Therefore, modulating eNOS uncoupling by stabilizing eNOS activity, enhancing its substrate, cofactors, and transcription, and reversing uncoupled eNOS are attractive therapeutic approaches to improve endothelial function. This review provides an extensive overview of the important role of eNOS uncoupling in the pathogenesis of endothelial dysfunction and the potential therapeutic interventions to modulate eNOS for tackling endothelial dysfunction.
Original languageEnglish
Pages (from-to)E481-E495
JournalAmerican Journal of Physiology : Endocrinology and Metabolism
Volume302
Issue number5
DOIs
Publication statusPublished - Mar 2012

Keywords

  • endothelial dysfunction
  • nitric oxide synthase
  • nitric oxide synthase uncoupling
  • superoxide

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