Our previous studies indicated that HSF1 acted as a repressor to suppress IGF-IIR expression and prevented hypertension-induced heart failure via binding to the heat shock element (HSE) located in the (nt −733 to −706) region of the Igf2r promoter.8 Intriguingly, another HSE was identified ~0.5 kb upstream of the Igf2r open reading frame that was not recognized by HSF1 (Supplementary Figure 1A). Here, IGF2R is linked to heart failure.