Overview of targeting endothelial CB1 by water-soluble isoflavone monophosphates to ameliorate disturbed flow-induced atherosclerotic endothelial dysfunction.
Despite advances in lipid-lowering and anti-inflammatory therapies, atherosclerosis remains a major global health challenge. Current treatments mainly target systemic risk factors, while the diseased vascular wall, especially endothelial cells exposed to disturbed blood flow, remains insufficiently addressed.
Researchers at National Taiwan University found that CB1 receptors are markedly upregulated in human and mouse atherosclerotic lesions and in endothelial cells exposed to disturbed flow, driven by transcription factors KLF4, Spi1, and ZNF610. The study is published in Journal of Biomedical Science.
They also identified the soy isoflavone daidzein as a novel CB1 antagonist. To improve drug properties, the team developed prodrugs genistein 7-O-phosphate (G7P) and daidzein 7-O-phosphate (D7P). Pharmacological or genetic inhibition of CB1 reduced endothelial inflammation, oxidative stress, and endothelial-to-mesenchymal transition, while oral G7P and D7P significantly decreased plaque formation in mouse models.
“These results highlight endothelial CB1 as a mechanosensitive driver of vascular dysfunction and suggest that soy-derived isoflavone prodrugs could offer a promising oral therapy for atherosclerosis,” says corresponding author Prof. Tzu-Tang Wei at Department and Graduate Institute of Pharmacology, National Taiwan University.
Postdoctoral scholar Dai‑Jung Chung is the first author. Other authors from National Taiwan University include Shao‑Peng Chen, Wei‑Hsuan Liu, Chia‑Yu Liu, Nan‑Wei Su, Chen Hsu, Hsin‑Ya Tsai, Kai‑Chien Yang, and Cho‑Kai Wu. Additional contributors from Academia Sinica are Sheng‑Wei Lin and Jiun‑Jie Shie, while Ming‑Tao Zhao represents Ohio State University.
Prof. Tzu-Tang Wei's email address: [email protected]
