Hyperhomocysteinemia increases arterial permeability and stiffness in mice

Area of Science:

• Cardiovascular Science
• Metabolic Disorders
• Vascular Biology

Background:

• Hyperhomocysteinemia (HHcy) is linked to arterial dysfunction.
• Previous studies suggest folate depletion affects arterial permeability and stiffness.
• The independent role of HHcy in these vascular changes requires further investigation.

Purpose of the Study:

• To determine if HHcy independently increases arterial permeability and stiffness in mice.
• To investigate the mechanisms underlying acute HHcy-induced arterial permeability changes.

Main Methods:

• Mice were subjected to chronic HHcy via L-methionine supplementation.
• Arterial permeability was measured using dextran accumulation.
• Arterial stiffness was assessed using elastography.
• Acute HHcy effects on permeability were studied in vitro with xanthine/xanthine oxidase and DL-homocysteine, with interventions including nitric oxide donors and scavengers.

Main Results:

• Chronic HHcy significantly increased carotid arterial permeability and aortic stiffness in mice.
• Acute exposure to DL-homocysteine markedly increased arterial permeability.
• This increase was attenuated by nitric oxide donors and superoxide scavengers, indicating a role for oxidative stress.

Conclusions:

• HHcy is an independent risk factor for increased arterial permeability and stiffness.
• Acute HHcy exacerbates arterial permeability through superoxide anion generation, reducing nitric oxide bioavailability.
• These findings highlight HHcy's detrimental effects on vascular health.