Famciclovir Ameliorates Platelet Activation and Thrombosis by AhR-Regulated Autophagy

Area of Science:

• Cardiovascular Science
• Pharmacology
• Molecular Biology

Background:

• Cardiovascular diseases (CVDs) present significant global health challenges.
• Current antiplatelet therapies have limitations and side effects.
• Novel therapeutic targets and drugs are needed to manage CVDs.

Purpose of the Study:

• To identify novel therapeutic targets for CVDs.
• To investigate the potential of famciclovir as an aryl hydrocarbon receptor (AhR) inhibitor for treating CVDs.
• To evaluate the efficacy of famciclovir in reducing platelet activation and thrombosis.

Main Methods:

• Screening of CVD targets using the Gene Card database.
• Computer-aided drug screening and molecular docking to identify potential inhibitors.
• In vitro experiments on thrombin-stimulated platelets to assess AhR expression, platelet activation, mitochondrial damage, and oxidative stress.
• In vivo studies using FeCl3-induced carotid arterial thrombosis and middle cerebral artery occlusion models.

Main Results:

• AhR was identified as a potential target linked to CVDs.
• Famciclovir was identified as a potential AhR inhibitor.
• Famciclovir suppressed AhR expression and platelet activation, reducing mitochondrial damage and oxidative stress.
• Oral famciclovir inhibited thrombin-induced platelet aggregation without affecting coagulation or thrombolysis.
• Famciclovir mitigated arterial and cerebral thrombosis in vivo.

Conclusions:

• Inhibiting AhR expression with famciclovir effectively reduces platelet activation and thrombosis.
• Famciclovir demonstrates promise as a potential therapeutic strategy for cardiovascular diseases.
• This study highlights a novel mechanism for managing CVDs by targeting AhR.