The lean diabetic patients with heart failure with preserved ejection fraction (HFpEF) in Asia suffer from adverse clinical outcomes and poor life quality. The suitable animal models are urgently needed for mechanistic study and therapeutic innovations. Our study reports that lipodystrophic mice with seipin depletion are lean, diabetic, and recapitulate major manifestations of clinical HFpEF, thereby clarifying that lean diabetes per se may produce HFpEF characteristics. We further demonstrate that increased cardiac titin phosphorylation and reactive interstitial fibrosis associated with neutrophil extracellular traps lead to left ventricular stiffness and suggest that both pathways may be potential therapeutic targets in Asian HFpEF patients.
Keywords: Ctrl, control (mice); EDPVR, end-diastolic pressure–volume relationship; HFpEF, heart failure with preserved ejection fraction; IQR, interquartile range; LA, left atrial; LV, left ventricular; NET, neutrophil extracellular trap; PEVK, proline, glutamate, valine, and lysine; SKO, seipin knockout; fibrosis; heart failure with preserved ejection fraction; neutrophil; seipin; titin.
© 2019 The Authors.