Suberanilohydroxamic Acid as a Pharmacological Kruppel‐Like Factor 2 Activator That Represses Vascular Inflammation and Atherosclerosis

BackgroundKruppel‐like factor 2 (KLF2) is an important zinc‐finger transcription factor that maintains endothelial homeostasis by its anti‐inflammatory, ‐thrombotic, ‐oxidative, and ‐proliferative effects in endothelial cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases. Methods and ResultsHigh‐throughput drug screening based on KLF2 promoter luciferase reporter assay was performed to screen KLF2 activators. Real‐time PCR and western blot were used to detect gene and protein expression. Identified KLF2 activator was orally administered to ApoE−/− mice to evaluate anti‐atherosclerotic efficacy. By screening 2400 compounds in the Spectrum library, we identified suberanilohydroxamic (SAHA) acid, also known as vorinostat as a pharmacological KLF2 activator through myocyte enhancer factor 2. We found that SAHA exhibited anti‐inflammatory effects and attenuated monocyte adhesion to en...