FAP in cardiovascular pathophysiology: Advances in non-invasive imaging and therapeutic targeting for myocardial fibrosis.

Fibroblast activation protein (FAP), a key biomarker of activated fibroblasts in pathological tissue remodeling, is up-regulated in injured myocardium, driving cardiac fibrosis and adverse ventricular dysfunction. FAP's specificity for activated fibroblasts enables its use as a target for non-invasive molecular imaging, risk stratification and therapeutic efficacy. Radiolabeled FAP inhibitors (FAPIs), allow positron emission tomography to visualize fibroblast activity in myocardial infarction, non-ischemic cardiomyopathies, heart failure, atherosclerosis, and cardiotoxicity. Therapeutically, FAP-targeted strategies such as 177Lu-FAPI, chimeric antigen receptor-engineered natural killer cells and T cells, FAP vaccines show promise in mitigating fibrosis. The integration of FAP-targeted imaging and therapy offers a paradigm for precision medicine in cardiac fibrosis management. Here we synthesize current translational and clinical evidence for FAPI PET tracers in cardiovascular disease and succinctly outline emerging FAP-targeted anti-fibrotic strategies.