IGFBP7 and Heart Failure: From Senescence Biomarker to Therapeutic Target

To integrate clinical and preclinical evidence on insulin-like growth factor-binding protein-7 (IGFBP7) in heart failure (HF) and identify key priorities for advancing IGFBP7-targeted therapies toward human translation. Circulating IGFBP7 is strongly associated with HF development, diastolic dysfunction, and disease progression across HF phenotypes. Preclinical studies show that genetic or pharmacologic inhibition of IGFBP7 attenuates cardiac remodelling, reduces cardiomyocyte senescence, and ameliorates cardiac dysfunction in murine HF models. Apparent mechanistic discrepancies between studies likely reflect cell-specific actions: cardiomyocyte-derived IGFBP7 activates IGF-1 receptor signalling, promoting cardiomyocyte hypertrophy and senescence, whereas endothelial-derived IGFBP7 inhibits cardiomyocyte insulin receptor signalling, impairing metabolic homeostasis. IGFBP7 is a senescence-associated biomarker linked to HF development, diastolic dysfunction, and HF progression. Preclinical studies converge on the conclusion that IGFBP7 inhibition attenuates cardiac remodelling and ameliorates cardiac dysfunction in experimental HF, positioning IGFBP7 as a promising therapeutic target. Ongoing research into IGFBP7-targeted strategies may expand HF treatment beyond conventional hemodynamic and neurohormonal interventions by directly addressing the biology of cardiovascular ageing and senescence-driven myocardial dysfunction.