Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species

• DOI: 10.1186/s13287-023-03615-x
• Publication Date: 2024-01-17T03:02:23Z
• Authors: Juntao Fang; Qiangbing Yang; Renée G. C. Maas; Michele Buono; Bram Meijlink; Dyonne Lotgerink ...; Ernest Diez Benav...; Michal Mokry; Alain van Mil; Li Qian; Marie-José Goumans; Raymond Schiffelers; Zhiyong Lei; Joost P. G. Sluijter
• Keywords: Reprogramming

Abstract Background After myocardial infarction, the lost myocardium is replaced by fibrotic tissue, eventually progressively leading to dysfunction. Direct reprogramming of fibroblasts into cardiomyocytes via forced overexpression cardiac transcription factors Gata4, Mef2c, and Tbx5 (GMT) offers a promising strategy for repair. The limited efficiency this approach, however, remains significant challenge. Methods We screened seven capable improving direct both mice human evaluating small molecules known be involved in cardiomyocyte differentiation or promoting human-induced pluripotent stem cell reprogramming. Results found that vitamin C (VitC) significantly increased when added GMT-overexpressing from 2D 3D model. observed increase reactive oxygen species (ROS) generation upon Doxy induction, ROS was subsequently reduced VitC treatment, associated with efficiency. However, treatment dehydroascorbic acid, structural analog but lacking antioxidant properties, no difference observed, suggesting effect enhancing partly dependent its properties. Conclusions Our findings demonstrate supplementation enhances reprogramming, partially suppressing production presence GMT. Graphical abstract