Abstract
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.
Highlights
Compensatory adaptation occurs early in response to high blood pressure [1]
Exosomes were isolated from the cultured medium of embryonic stem cells (ESCs). qNano analysis showed that most exosomes were in the range of 50–125 nm in size (Figure 1A)
Proteomic analysis of ESC-derived exosomes showed that EC-derived exosomes contained hundreds of proteins, among which FGF2 was highly abundant, ranking in the top ten of all proteins detected within exosomes (Figures 2A,B)
Summary
Compensatory adaptation occurs early in response to high blood pressure [1]. Persistent high blood pressure results in cardiac remodeling, which eventually leads to heart failure [2, 3]. Inadequate blood supply accelerates the transition from compensatory cardiac hypertrophy to heart failure [4, 5]. Previous studies have demonstrated the potential of embryonic stem cells (ESCs) in rescuing injured hearts, which is due to their considerable differentiation ability [6,7,8]. 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. Their effects in hypertension-induced heart failure are still unknown
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