Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide

Area of Science:

• Cardiovascular Science
• Neurology
• Nephrology

Background:

• Hyperhomocysteinemia (HHcy) is increasingly linked to various vascular disorders, including cerebral, coronary, and renal diseases, as well as hypertension.
• Impaired nitric oxide (NO) synthesis and function, due to factors like asymmetric dimethylarginine and reactive oxygen species, are key mechanisms in HHcy-related vascular dysfunction.
• Reduced NO bioavailability and brain hypoperfusion are implicated in the pathogenesis of dementia and Alzheimer's disease.

Purpose of the Study:

• To elucidate the role of hyperhomocysteinemia in the pathogenesis of vascular circulatory disorders.
• To explore the mechanisms by which HHcy impairs endothelial function and contributes to diseases like dementia and Alzheimer's.
• To identify preventive strategies against HHcy-induced circulatory failures.

Main Methods:

• Review of existing evidence linking HHcy to vascular pathologies.
• Analysis of the molecular mechanisms involving nitric oxide (NO) dysfunction and oxidative stress.
• Investigation of the impact of homocysteine (Hcy) on endothelial function and cerebral circulation.

Main Results:

• HHcy is a significant factor in the development of cerebral, coronary, renal circulatory disorders, and hypertension.
• Impaired NO synthesis and action, along with increased oxidative stress, mediate HHcy-induced vascular damage.
• HHcy contributes to dementia and Alzheimer's disease through reduced brain circulation and amyloid-β production, creating a detrimental cycle.

Conclusions:

• Hyperhomocysteinemia is a critical risk factor for multiple vascular diseases and hypertension.
• Strategies to improve NO bioavailability, reduce oxidative stress, and manage homocysteine levels are crucial for preventing HHcy-related vascular complications.
• Lifestyle modifications, favorable dietary habits, and supplementation with folic acid and vitamins B6/B12 are beneficial in mitigating HHcy-induced circulatory failures.