Intravenous administration of EV@miR-155 significantly improved cardiac function and reduced myocardial fibrosis and hypertrophy without inducing systemic toxicity (P < 0.05) in a mouse model.
Does EV@miR-155 improve cardiac function and reduce myocardial fibrosis and hypertrophy in a mouse model of Ang II-induced cardiac injury?
Intravenous delivery of EV@miR-155 leverages natural hepatic tropism to suppress FGF21 production, establishing a liver-heart crosstalk axis that improves cardiac function and reduces fibrosis in a mouse model of cardiac injury.
p-value: p=<0.05
Extracellular vesicles (EVs) hold great potential to deliver microRNAs (miRNAs) in vivo; however, its preferential hepatic accumulation after systemic administration hinders the therapeutic efficacy of miRNAs. Inter-organ communication via endocrine factors is crucial for maintaining physiological homeostasis. Herein, this study leveraged liver-heart crosstalk to overcome the hepatic tropism of EVs and reframe it as a therapeutic advantage for cardiac injury. In a mouse model of angiotensin II (Ang II)-induced cardiac injury, liver tissues showed distinct changes in inflammation-related proteins compared with saline-treated controls, indicating hepatic involvement in cardiac injury. To establish a liver-heart crosstalk-based therapeutic approach, EV@miR-155 were prepared by loading miRNA-155 into mesenchymal stem cell-derived EVs. After intravenous administration, EV@miR-155 predominantly accumulated in the liver, increased hepatic miRNA-155 levels, and remodeled the hepatic microenvironment. This remodeling suppressed PPARα-mediated production of fibroblast growth factor 21 (FGF21), a hepatokine implicated in cardiac pathophysiology, thereby establishing a liver-heart crosstalk axis. Remarkably, EV@miR-155 treatment significantly improved cardiac function and reduced myocardial fibrosis and hypertrophy without inducing systemic toxicity (P < 0.05). Therefore, this study provides a conceptual shift by transforming the natural hepatic tropism of EVs-traditionally regarded as a delivery limitation-into a therapeutic route that enables liver-heart crosstalk-mediated cardiac repair.
Kang et al. (Mon,) conducted a other in Angiotensin II (Ang II)-induced cardiac injury. EV@miR-155 vs. Saline was evaluated on Cardiac function, myocardial fibrosis, and hypertrophy (p=<0.05). Intravenous administration of EV@miR-155 significantly improved cardiac function and reduced myocardial fibrosis and hypertrophy without inducing systemic toxicity (P < 0.05) in a mouse model.
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