Acute hyperhomocysteinemia induces microvascular and macrovascular endothelial dysfunction

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Vascular Biology

Background:

• Hyperhomocysteinemia (Hhcy) is linked to endothelial dysfunction and reduced nitric oxide (NO) bioavailability.
• Increased vascular oxidant stress contributes to Hhcy-induced endothelial dysfunction.
• Previous studies focused on conductance arteries; effects on resistance vessels remain unclear.

Purpose of the Study:

• To investigate the impact of acute Hhcy on both macrovascular and microvascular endothelial function (EF) in humans.
• To assess changes in endothelium-dependent vasodilation in brachial and forearm resistance vessels.

Main Methods:

• Macrovascular EF assessed via brachial artery flow-mediated dilation using vascular ultrasound.
• Microvascular EF measured by forearm skin perfusion response to acetylcholine via laser Doppler fluxmetry.
• Acute Hhcy induced by oral methionine challenge in 11 healthy subjects.

Main Results:

• Oral methionine increased homocysteine levels approximately 5.1-fold.
• Significant reduction in brachial artery flow-mediated dilation (8.1% to 3.6%).
• Significant decrease in acetylcholine-stimulated forearm skin blood flow (9.2-fold to 7.8-fold).

Conclusions:

• Acute hyperhomocysteinemia significantly impairs macrovascular endothelial function in humans.
• Acute hyperhomocysteinemia also impairs microvascular endothelial function in humans.
• Findings highlight Hhcy's detrimental effects on both large and small blood vessels.