Embryonic stem cell-derived exosomes attenuate transverse aortic constriction induced heart failure by increasing angiogenesis

Extracellular Vesicles

Pang, Yanan, Minglu Ma, Dong Wang, Jiacun Xia, Xinyue Wang, Lei Hou, Zhiguo Wang, and Xun Li. "Embryonic stem cell-derived exosomes attenuate transverse aortic constriction induced heart failure by increasing angiogenesis." Frontiers in Cardiovascular Medicine 8 (2021).

Background: Although there are concerns regarding their clinical use, embryonic stem cells (ESCs) hold a great promise for cardiac repair. Exosomes deriving from ESCs constitute a promising alternative for heart restoration. However, their effects in hypertension-induced heart failure are still unknown. Objective and Methods: To investigate the effects of ESCs-derived exosomes on hypertension-induced heart failure and the underlying mechanisms, sustained transverse aortic constriction (TAC) was performed on 8-week-old C57BL/6 male mice. After 1 months, ESCs-derived exosomes were isolated and injected intravenously once a week for 6 weeks. Echocardiography, wheat germ agglutinin (WGA), Masson staining, immunohistochemistry, and tube formation assays were all involved in our study. Results: Proteomics analyses revealed that ESC-derived exosomes contain FGF2 protein. Tube formation induced by these exosomes could be inhibited by FGF2R siRNA interference. ESCs-derived exosomes evidently attenuated TAC-induced heart failure, improving cardiac function and promoting myocardial angiogenesis which can be attenuated by selective FGF2 inhibitor AZD4547. Conclusions: ESC-derived exosomes attenuate TAC-induced heart failure mostly by promoting myocardial angiogenesis. FGF2 signaling plays a vital role in the myocardial angiogenesis induced by ESC-derived exosomes. Keywords: embryonic stem cells, exosomes, angiogenesis, transverse aortic constriction, heart failure

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