Homocysteine impairs coronary microvascular dilator function in humans

Area of Science:

• Cardiovascular Physiology
• Metabolic Disorders
• Diagnostic Imaging

Background:

• Hyperhomocysteinemia is linked to impaired vasodilation in peripheral arteries.
• Its impact on the coronary circulation remains largely unknown.
• Understanding this relationship is crucial for cardiovascular health.

Purpose of the Study:

• To investigate the effect of hyperhomocysteinemia on coronary microvascular dilator function.
• To test the hypothesis that elevated homocysteine levels adversely affect coronary blood flow regulation.
• To elucidate the role of nitric oxide (NO) in this process.

Main Methods:

• Positron emission tomography (PET) was used to measure myocardial blood flow (MBF) in 18 healthy subjects.
• A double-blind, crossover design involved inducing hyperhomocysteinemia with methionine and measuring MBF response to adenosine.
• Brachial artery ultrasonography assessed flow-mediated dilation, and NG-monomethyl-l-arginine (l-NMMA) was used to inhibit nitric oxide synthase.

Main Results:

• Hyperhomocysteinemia significantly reduced the dose-response of MBF to adenosine, particularly at low doses (p < 0.05).
• Flow-mediated brachial artery vasodilation was also impaired during hyperhomocysteinemia (p < 0.05).
• Inhibition of NO synthesis with l-NMMA blunted the MBF response to adenosine, confirming NO's role.

Conclusions:

• Acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation.
• This impairment is attributed to a reduction in nitric oxide (NO) bioavailability.
• The findings highlight a potential mechanism linking elevated homocysteine to cardiovascular risk.