Conclusions
Ang II-induced cardiomyocyte injury leads to cardiac hypertrophy and fibrosis through the release of exosomes carrying Shh signaling. The suppression of exosome secretion or the Shh pathway could offer new strategies for treating HF.
Methods
Eight-week-old male mice were divided into three groups: a control group, an Ang II group receiving angiotensin II (Ang II) infusion for 4 weeks, and an Ang II + DMA group receiving Ang II and dimethyl amiloride (DMA) infusion. This study examined the associations between cardiac injury, exosomes, and their substrate Shh. Furthermore, we conducted cellular experiments to assess the effects of Ang II-induced injury in primary cardiomyocytes on other cardiomyocytes and fibroblasts, and to test the therapeutic effects of the exosome inhibitor DMA and the Shh signaling inhibitor cyclopamine (CPN).
Results
Ang II-induced cardiac hypertrophy and fibrosis, which were accompanied by exosome secretion and Shh upregulation in vivo. DMA relieved these cardiac lesions. Furthermore, cellular experiments revealed that Ang II-induced cardiomyocytes hypertrophy and activated cardiac fibroblasts by promoting the release of exosomes containing Shh/N-Shh/Gli1. Both DMA and CPN nullified fibroblast activation and proliferation. Conclusions: Ang II-induced cardiomyocyte injury leads to cardiac hypertrophy and fibrosis through the release of exosomes carrying Shh signaling. The suppression of exosome secretion or the Shh pathway could offer new strategies for treating HF.