Liu Wenqiang, Wu Xuekun, Zeng Wenshu, Chandy Mark, Wu Joseph C
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Western University, London, Ontario, Canada.
Trends Pharmacol Sci. 2025 Nov;46(11):1072-1090. doi: 10.1016/j.tips.2025.07.016. Epub 2025 Aug 27.
Cardiac fibrosis is a hallmark of cardiovascular and systemic diseases that arises in diverse pathological contexts such as inflammation, metabolic stress, and mechanical overload. Despite its clinical relevance, no FDA-approved therapies directly target cardiac fibrotic remodeling, highlighting persistent challenges in disease organization, model fidelity, and translational strategy. Recent advances in human induced pluripotent stem cell (iPSC)-derived models, engineered heart tissues, and in vivo systems have uncovered new fibrotic drivers, including immune-stroma crosstalk, metabolic reprogramming, and mechanotransduction, that are reshaping therapeutic development. This review synthesizes emerging molecular mechanisms, experimental models, and preclinical and clinical investigations of antifibrotic agents. Distinct from previous reviews, we emphasize cross-contextual alignment to support the development of precision antifibrotic therapy for cardiac fibrosis.
