Influences of lysine‐specific demethylase 1 inhibitors on NO synthase–Kruppel‐like factor pathways in human endothelial cells in vitro and zebrafish (Danio rerio) larvae in vivo

• DOI: 10.1002/jat.4512
• Publication Date: 2023-07-06T04:44:24Z
• Authors: Jialin Yuan; Ruiman Que; Weichao Zhao; Fengmei Song; Yi Cao; Bin Yu
• Keywords: Danio; KLF2; Demethylase

Lysine-specific demethylase 1 (LSD1) inhibitors are being developed for cancer therapy, but their bioeffects on vasculatures not clear. In this study, we compared the influences of ORY-1001 (an LSD1 inhibitor advanced into clinical trials) and 199 (a novel recently by us) to human umbilical vein endothelial cells (HUVECs) in vitro further verified zebrafish (Danio rerio) larvae vivo. The results showed that up 10 μM or did significantly affect cellular viability HUVECs substantially reduced release inflammatory interleukin-8 (IL-8) IL-6. signaling molecule vasculatures, NO, was also increased HUVECs. As mechanism, protein levels NO synthase (eNOS) p-eNOS, regulators Kruppel-like factor 2 (KLF2) KLF4, were after drug treatment. vivo, 24 h treatment with 100 nM blood speed without changing morphologies locomotor activities larvae. expression il8 promoted klf2a nos model. These data show toxic capable inhibit responses function vessels through up-regulation NOS-KLF pathway.