This study demonstrated that insulin resistance compromises the pentose phosphate pathway and impairs LVAD-mediated cardiac recovery, explaining why diabetic patients have worse myocardial recovery during mechanical support.
BACKGROUND:End-stage heart failure (HF) remains a major global health challenge, and left ventricular assist devices (LVADs) represent an important therapeutic option. LVAD-mediated mechanical unloading improves cardiac function and promotes myocardial recovery in many patients with HF. How cardiac unloading by LVADs leads to myocardial recovery and whether impairment of these processes underlies the limited myocardial recovery benefit in obese patients remain poorly understood.METHODS:Patients with HF with LVADs were recruited for an investigation of the correlation between patients’ body mass index and their response to LVAD-mediated myocardial recovery. Moreover, a mouse model of heterotopic cervical heart transplantation was used to simulate LVAD unloading. Single-nucleus RNA sequencing and stable-isotope tracing metabolomics were performed to explore the changes of signaling pathways and metabolic processes in unloaded hearts. In vitro cyclic stretch assays were used to evaluate h
