Hyperhomocysteinemia and Cardiovascular Disease: Is the Adenosinergic System the Missing Link?

Area of Science:

• Cardiovascular Science
• Biochemistry
• Immunology

Background:

• Hyperhomocysteinemia (HHCy) is linked to cardiovascular disease (CVD), stroke, and myocardial infarction.
• Current HCy-lowering therapies show limited efficacy in managing CVD inflammation and risk.
• Hydrogen sulfide (H2S), an HCy metabolite, is recognized for its cardioprotective effects.

Purpose of the Study:

• To investigate the paradoxical role of HCy and its metabolite H2S in cardiovascular disease progression.
• To explore the potential mechanism by which HHCy exacerbates CVD, contrary to the cardioprotective role of H2S.

Main Methods:

• Review of recent scientific data and proposed mechanisms.
• Analysis of the interaction between HCy, H2S, adenosine A2A receptors, and cellular responses in CVD.

Main Results:

• HHCy may increase H2S production, paradoxically worsening CVD.
• Elevated H2S may downregulate adenosine A2A receptors on immune and cardiovascular cells.
• This downregulation is proposed to cause inflammation and ischemia, contributing to CVD.

Conclusions:

• HHCy might exacerbate CVD through increased H2S production, leading to reduced adenosine A2A receptor expression.
• This mechanism offers a novel perspective on the pathophysiology of HHCy in cardiovascular conditions.
• Further research is warranted to validate the role of H2S and adenosine A2A receptors in HHCy-related CVD.