Conditional knockout of IGFBP6 in cardiac fibroblasts and myofibroblasts markedly attenuated post-myocardial infarction fibrotic remodeling, ventricular dysfunction, and isoproterenol-induced cardiac hypertrophy.
Fibroblast-derived IGFBP6 drives cardiac fibrosis via the EGR1-MFAP4 axis, presenting a potential novel therapeutic target for cardiac remodeling disorders.
Our study identifies fibroblast-derived IGFBP6 as a novel regulator of cardiac fibrosis through the EGR1-MFAP4 signaling axis, driving myofibroblasts differentiation and adverse remodeling. Targeting this pathway may offer therapeutic potential for cardiac remodeling disorders.
Cheng et al. (2025) studied Cardiac fibrosis and myocardial infarction (n=56). Cardiac fibroblast and myofibroblast-specific IGFBP6 knockout vs. IGFBP6 f/f (wild-type) mice was evaluated on Cardiac fibrosis, ventricular dysfunction, and infarct size. Conditional knockout of IGFBP6 in cardiac fibroblasts and myofibroblasts markedly attenuated post-myocardial infarction fibrotic remodeling, ventricular dysfunction, and isoproterenol-induced cardiac hypertrophy.