Targeting mechanosensitive cannabinoid receptor 1 with isoflavone prodrugs attenuates atherosclerotic endothelial dysfunction.

ABSTRACT:

Background

Despite therapeutic advances, atherosclerosis remains a major global health challenge. Most current treatments target systemic risk factors rather than the diseased vascular wall. Our previous work identified genistein, a soy isoflavone, as a cannabinoid receptor 1 (CB1) antagonist capable of suppressing CB1-mediated vascular inflammation and atherosclerosis. However, its poor water solubility and low oral bioavailability limit clinical application.

Purpose

We aimed to develop water-soluble, orally bioavailable CB1 antagonists for atherosclerosis and to investigate the role of endothelial CB1 in hemodynamic regulation.

Methods

RNA-sequencing datasets from the NCBI GEO repository were analyzed to assess CB1 expression in atherosclerotic patients. Apolipoprot

SUBMITTER: Chung DJ 

PROVIDER: S-EPMC12822132 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature