Vascular endothelium dysfunction: a conservative target in metabolic disorders

Area of Science:

• Vascular biology
• Endocrinology
• Metabolic disorders

Background:

• The vascular endothelium is crucial for regulating local vascular homeostasis, including nutrient transport, angiogenesis, vascular tone, and permeability.
• It maintains a delicate balance between vasodilatation and vasoconstriction, and procoagulant and anticoagulant mechanisms.

Purpose of the Study:

• To investigate the role of the vascular endothelium in the context of metabolic disorders.
• To elucidate the cellular and molecular mechanisms linking metabolic conditions to endothelial dysfunction.

Main Methods:

• The study reviews mechanisms by which diabetes mellitus, hyperhomocysteinemia, hypercholesterolemia, and hypertension affect endothelial function.
• It examines the impact of these conditions on endothelial nitric oxide synthase (eNOS) activity and expression, oxidative stress, and the bioavailability of nitric oxide.

Main Results:

• Diabetes mellitus leads to endothelial dysfunction via aldose reductase, polyol pathway, and advanced glycation end-products, affecting eNOS.
• Hyperhomocysteinemia increases LDL oxidation and nitric oxide degradation, while hypercholesterolemia and hypertension elevate oxidative stress and reduce nitric oxide bioavailability.
• These conditions disrupt the integrity of the vascular endothelium by altering eNOS activity and expression.

Conclusions:

• Metabolic disorders disrupt the phosphorylation and dephosphorylation balance of kinases, modulating the L-arginine/eNOS pathway.
• This modulation results in vascular endothelium dysfunction, impacting overall vascular health.