TY - JOUR
T1 - Tackling endothelial dysfunction by modulating NOS uncoupling
T2 - New insights into its pathogenesis and therapeutic possibilities
AU - Kietadisorn, Rinrada
AU - Juni, Rio P.
AU - Moens, An L.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Endothelial dysfunction
KW - Nitric oxide synthase
KW - Nitric oxide synthase uncoupling
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=84857438179&partnerID=8YFLogxK
U2 - https://doi.org/10.1152/ajpendo.00540.2011
DO - https://doi.org/10.1152/ajpendo.00540.2011
M3 - Review article
C2 - 22167522
SN - 0193-1849
VL - 302
SP - E481-E495
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 5
ER -