A high-throughput analysis of novel anti-fibrotics in human adult cardiac fibroblasts

Myocardial fibrosis, a hallmark of heart failure (HF), contributes to disease progression and mortality by impairing cardiac function. Despite the identification of potential anti-fibrotic molecules, there is a lack of effective pharmacological interventions for cardiac fibrosis due to poor translational relevance and limited clinical success. In vitro culture models using human cardiac fibroblasts (hCF) provide a cost-effective and scalable approach for high-throughput drug screening, particularly when coupled with artificial intelligence (AI)-assisted imaging technologies. In this study, we developed a novel high-throughput 2D screening platform to identify new anti-fibrotic compounds targeting hCF. Using this approach, we have successfully identified novel molecules with potential anti-fibrotic activity, offering new therapeutic avenues for cardiac fibrosis and other fibrotic disorders. • Cardiac fibrosis is a major contributor to heart failure progression. • Effective treatments for cardiac fibrosis remain limited. • A new high-throughput screening platform for fibroblast activation was developed. • Three classes of new candidate anti-fibrotics were uncovered.