Targeting Cardiac Proteotoxicity

There is a preponderance of evidence that the progression from a large subset of human heart diseases to heart failure (HF) involves increased proteotoxic stress (IPTS); and experimental studies are demonstrating that targeting IPTS could be a novel and effective strategy for HF intervention, including both HF with reduced ejection fraction (EF) and HF with preserved EF. However, the significance of proteotoxicity in cardiac pathophysiology remains underappreciated and, importantly, none of the current clinical therapies for HF are intended to target IPTS yet, calling for increasing our effort to educate the biomedical community on this nascent and exciting field.

In the past several years, exciting new progresses have been made at multiple levels (e.g., proteomics, molecular/cell biology, and integrative physiology) regarding the underlying causes and mechanisms of action of IPTS in diseased hearts as well as novel strategies to facilitate the clearance of toxic protein species by both proteasomes and lysosomes. This Research Topic is intended to timely highlight these cutting-edge multi-disciplinary sciences, stimulate new ideas, entice more researchers to join the field, and move forward this underappreciated but highly significant field. Both Original Research and Review articles are welcomed.