Exosomal hsa_circ_0007047 Attenuates Pos-myocardial Infarction Remodeling by Promoting Angiogenesis via miR-1178-3p/PDPK1 Axis

Abstract Emerging studies indicate that exosomes and their inner noncoding RNAs, especially circular RNAs (circRNAs), play key roles in gene regulatory network and cardiovascular repair. However, our understanding of exosomal circRNAs on cardiac remodeling after myocardial infarction (MI) remains limited. In the present study, exosomes were harvested from the serum of patients with and without postinfarction cardiac remodeling. The results showed that the level of hsa_circ_0007047 was significantly downregulated in serum exosome of patients with the adverse cardiac remodeling when compared with those without post-MI remodeling or normal subjects. Loss-of-function approaches in vitro established that exosomal hsa_circ_0007047 robustly promoted angiogenesis and stimulated of cultured human vascular smooth muscle cells proliferation and migration. Accordingly, overexpression of exosomal hsa_circ_0007047 in mice significantly attenuated MI-induced myocardial fibrosis and left ventricular dysfunction, accompanied by a larger functional capillary network at the border zone. Further exploration of the downstream target gene indicated that hsa_circ_0007047 acts as a competing endogenous RNA by directly binding to miR-1178-3p and thereby inducing transcription of its target gene phosphoinositide-dependent kinase-1 (PDPK1), a critical positive regulatory factor of angiogenesis. Together, our results revealed that exosomal hsa_circ_0007047 attenuated detrimental post-MI remodeling via miR-1178-3p/PDPK1 axis, which facilitated revascularization, ultimately improved the cardiac function.