Unraveling the role of NHE9 in Cardiac Repair: From Endosomal pH Regulation to Exosome-Mediated Communication

Abstract

This study examines how NHE9, a sodium-proton exchanger, affects exosome production and cargo in cardiomyocytes. NHE9 helps reduce acid levels in endosomes, leading to more exosome release. When NHE9 is overexpressed, exosomes contain higher levels of proteins like CD63, Alix, Hsp70, and ubiquitinated proteins, indicating they carry more cargo. Additionally, it also shows that exosomes from cardiomyocytes with higher NHE9, especially under low oxygen (hypoxic) conditions, contain more HIF-1α, a marker of stress. These exosomes encourage macrophages to shift toward an anti-inflammatory state (M2), which is important for reducing oxidative stress in the heart. When NHE9 is reduced, both exosome production and their ability to influence macrophages are diminished. Overall, the findings suggest NHE9 plays a crucial role in controlling exosome release and their cargo, with potential therapeutic benefits for heart stress conditions