Human mesenchymal stem cell-derived exosomes facilitated CMEC angiogenesis and reduced infarction size in a rat myocardial infarction model by transferring miR-543 and downregulating COL4A1.
Does hMSCs-Exo containing miR-543 improve angiogenesis and reduce infarction size in a rat MI model?
hMSC-derived exosomes promote angiogenesis and reduce infarct size after myocardial infarction via the miR-543/COL4A1 axis in a rat model.
To explore the impact and mechanism of human mesenchymal stem cells (hMSCs) on the angiogenesis of cardiac microvascular endothelial cells (CMECs) after ischemia insult. Exosomes derived from hMSCs (hMSCs-Exo) were identified by Western blotting and labeled by PHK-67. CMECs were isolated from rat myocardial tissues. After hypoxic treatment, CMECs were cultured with hMSCs and exosome inhibitor (GW4869) or transfected with si-COL4A1 + miR-543 inhibitor. CMEC proliferation, migration, invasion, and angiogenesis were examined. Target genes of miR-543 were predicted and then were identified by dual luciferase assay. Myocardial infarction (MI) rat model established by suture occlusion was intravenously injected with hMSCs-Exo. Fluorescence microscope was applied to visualize exosomes in myocardial tissues. Infarction volume and pathologies of myocardial tissues were observed. Ki-67 and miR-543 expressions were detected. The isolated hMSC-Exo expressed TSG101, HSP70, and CD63. Hypoxia-treated CMECs cultured with hMSCs exhibited high proliferation, migration, invasion, and angiogenesis ability, while incubation with exosome inhibitor GW4969 offset the promoting effects of hMSCs on the proliferation, migration, invasion, and angiogenesis of CMECs. hMSCs transfected with miR-543 inhibitor brought CMECs weak viability and angiogenesis ability. CMECs transfected with si-COL4A1 and miR-543 inhibitor showed low proliferation, migration, invasion, and angiogenesis compared to those transfected with si-COL4A1 alone. hMSCs-Exo entered the myocardial tissues of MI rats. Injection of hMSCs-Exo in MI rats diminished infarction size, attenuated MI-induced injuries, and increased Ki-67 expression. hMSCs-Exo facilitates the proliferation, migration, invasion, and angiogenesis of CMECs through transferring miR-543 and downregulating COL4A1 expression.
Yang et al. (Fri,) conducted a other in Myocardial infarction (preclinical model). Human mesenchymal stem cell-derived exosomes (hMSCs-Exo) vs. Control conditions (exosome inhibitor GW4869, miR-543 inhibitor) was evaluated on CMEC proliferation, migration, invasion, angiogenesis, and infarction volume. Human mesenchymal stem cell-derived exosomes facilitated CMEC angiogenesis and reduced infarction size in a rat myocardial infarction model by transferring miR-543 and downregulating COL4A1.