In vivo, Mito Q@MMNv improved cardiac function and the inflammatory microenvironment, increasing left ventricular ejection fraction by 62% and shifting the M1/M2 ratio.
Does Mito Q@MMNv improve cardiac function and the inflammatory microenvironment in an in vivo model of myocardial ischemia-reperfusion injury?
A novel dual-targeted metabolic nanovesicle (Mito Q@MMNv) shows promise in a preclinical model for attenuating myocardial ischemia-reperfusion injury by targeting both cardiomyocytes and macrophages.
Abstract Reperfusion therapy for acute myocardial infarction is limited by myocardial ischemia‐reperfusion injury (MIRI). MIRI is primarily mediated by oxidative stress in cardiomyocytes, exacerbated by M1 macrophages in the inflammatory microenvironment. Synergistic therapies targeting cardiomyocytes with antioxidants and M1 macrophages with anti‐inflammatories have shown significant potential. Mitochondrial dysfunction is a unifying target for both cell types in MIRI; however, current nanoplatforms cannot simultaneously target them. Mito Q@MMNv is designed as a dual‐targeting nanovesicle for cardiomyocytes and macrophages. It scavenges reactive oxygen species in cardiomyocytes while restoring oxidative phosphorylation in M1 macrophages through cell‐selective metabolic reprogramming. In vivo, Mito Q@MMNv improves cardiac function and the inflammatory microenvironment: left ventricular ejection fraction increases by 62%, and the M1/M2 ratio shifts (delta cells increase 1.9‐fold). Synergistic activation of Keap1 and inhibition of NF‐κB attenuate inflammatory cascades while enhancing endogenous antioxidant defenses. Thus, this nano‐engineered platform offers an immunomodulatory therapy for inflammation control and tissue repair in MIRI, providing new insights into cardiovascular nanomedicine.
Xue et al. (Mon,) conducted a other in Myocardial ischemia-reperfusion injury (MIRI). Mito Q@MMNv was evaluated on Cardiac function and inflammatory microenvironment. In vivo, Mito Q@MMNv improved cardiac function and the inflammatory microenvironment, increasing left ventricular ejection fraction by 62% and shifting the M1/M2 ratio.