HOMOCYSTEINE AND CARDIOVASCULAR DISEASE - A CURRENT REVIEW

Area of Science:

• Cardiovascular Science
• Biochemistry
• Genetics

Background:

• Cardiovascular diseases, particularly ischemic heart disease, are the leading global cause of death.
• Atherosclerosis of the coronary arteries underlies over 98% of ischemic heart disease cases.
• Hyperhomocysteinemia, elevated homocysteine levels, is a significant risk factor for vascular damage and thrombotic complications.

Approach:

• This paper reviews evidence linking homocysteine metabolism and cardiovascular pathology.
• Mechanisms of homocysteine's adverse vascular effects are examined, including receptor activation and oxidative stress.
• The role of methylenetetrahydrofolate reductase (MTHFR) gene mutations in hyperhomocysteinemia and disease susceptibility is discussed.

Key Points:

• Homocysteine, an amino acid metabolite, can promote atherosclerosis and thrombosis when its plasma concentration is elevated.
• Adverse vascular effects involve Toll-like 4 receptor activation, N-methyl-d-aspartate receptor activation, increased reactive oxygen species (ROS), and impaired nitric oxide synthesis.
• Elevated ROS correlates with increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and adhesion molecules.
• MTHFR gene mutations impair homocysteine regulation, increasing predisposition to atherosclerosis, myocardial infarction, stroke, and coronary artery disease.

Conclusions:

• Hyperhomocysteinemia is a critical factor in the pathogenesis of numerous cardiovascular diseases.
• Understanding homocysteine's role provides targets for preventing and managing atherosclerosis and its complications.