Molecular mechanisms of endothelial dysfunction: from nitric oxide synthesis to ADMA inhibition.
Endothelial dysfunction symbolizes several pathological conditions, including altered anticoagulant and anti-inflammatory properties of the endothelium, impaired modulation of vascular growth, and dysregulation of vascular remodeling. Nevertheless, this term has been used commonly to refer to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide bioactivity. The clinical and scientific relevance of nitric oxide synthesis and bioavailability in endothelial dysfunction is based on the fact that it is a common factor in the pathogenesis of cardiovascular diseases. These alterations have been demonstrated in both animal models and humans, in the scope of dangerous pathological conditions such as cigarette smoking, hypertension, hypercholesterolemia, aging, diabetes, and heart failure. A decline in nitric oxide bioavailability may be caused by decreased expression of the endothelial nitric oxide synthase, a reduction of substrate or cofactors for this enzyme, alterations of cellular signaling, enzyme inhibition by asymmetric dimethyl arginine, and, finally, accelerated nitric oxide degradation by reactive oxygen species. The knowledge of the processes related to these alterations becomes of remarkable importance for understanding the generation of innovative and effective therapeutic strategies for cardiovascular diseases.
Bermúdez
Valmore
V
Endocrine and Metabolic Diseases Research Center, University of Zulia, School of Medicine, Maracaibo, Venezuela. Vbermudez@hotmail.com
Bermúdez
Fernando
F
Acosta
Guillermo
G
Acosta
Alejandro
A
Añez
Johnny
J
Andara
Carla
C
Leal
Elliuz
E
Cano
Clímaco
C
Manuel
Velasco
V
Hernández
Rafael
R
Israili
Zafar
Z
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III