Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.

ABSTRACT: Pathological cardiac hypertrophy is a major contributor to heart failure. The present study aims to elucidate the role and mechanisms of phosphoglycerate mutase 2 (PGAM2) in the pathogenesis of cardiac hypertrophy. PGAM2 expression was increased in both primary neonatal rat ventricular myocytes (NRVMs) and rat models in response to angiotensin II (Ang II). Downregulation of PGAM2 alleviated cardiac hypertrophy. Mechanistically, we found PGAM2 directly interacts with HSP90 through residues 319-323 and 622-629 in the middle and carboxy-terminal domain of HSP90 respectively. This interaction was further enhanced under Ang II stimulation. Additionally, in the presence of PGAM2, it competed with E3 ubiquitin ligase SYVN1 to interact with HSP90, effectively inhibiting the ubiquitination and degr

SUBMITTER: Li Y 

PROVIDER: S-EPMC11781161 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature