Lianmei Pu1, Xiangyun Kong2, Hong Li3, Xue He1. 1. Department of Emergency Cardiology, Beijing Anzhen Hospital, Capital Medical University Beijing 100029, P. R. China. 2. Department of General Medicine, Beijing Luhe Hospital, Capital Medical University Beijing 101100, P. R. China. 3. Cardiovascular Department, Beijing Anzhen Hospital, Capital Medical University Beijing 100029, P. R. China.
Abstract
AIM: Bone marrow-derived mesenchymal stem cells (BMMSCs) exert cardioprotective effects on myocardial infarction (MI). In this investigation, we elucidated the protective effects of BMMSCs-exosomes (Exo) expressing microRNA-30e (miR-30e) against heart failure (HF) in MI rats. METHODS: First, the differentially expressed miRNAs were analyzed using a miRNA-based microarray of MI. Subsequently, we overexpressed miR-30e in rat BMMSCs to isolate exosomes. A rat model with MI was developed and treated with Exo. Next, we examined the cardiac function of the rats, followed by the myocardial tissue extraction. HE, TUNEL and Masson's staining were used to assess the protective effects of exosomes against HF in rats. Subsequently, H9C2 cells exposed to OGD were further co-cultured with Exo. We used bioinformatics to predict the target mRNA of miR-30e and verified the binding relationship. Finally, we tested the expression and role of NF-κB p65/Caspase-9 signaling in myocardial tissues and cells. RESULTS: miR-30e was poorly expressed in myocardial tissues of MI rats. Moreover, treatment of rats with Exo overexpressing miR-30e ameliorated pathological damage, cardiomyocyte apoptosis, and fibrosis in rat myocardial tissues. Furthermore, miR-30e negatively regulated LOX1 expression, which was overexpressed in the MI rats, but further Exo treatment inhibited LOX1 expression. Moreover, Exo overexpressing miR-30e impaired the NF-κB p65/Caspase-9 signaling in myocardial tissues of MI rats. The NF-κB p65/Caspase-9 signaling inhibitor repressed the apoptosis and fibrosis of cardiomyocytes as well. CONCLUSION: Exosomal miR-30e from rat BMMSCs markedly inhibited LOX1 expression, thereby downregulating the activity of the NF-κB p65/Caspase-9 signaling and ameliorating HF after MI in rats. AJTR
AIM: Bone marrow-derived mesenchymal stem cells (BMMSCs) exert cardioprotective effects on myocardial infarction (MI). In this investigation, we elucidated the protective effects of BMMSCs-exosomes (Exo) expressing microRNA-30e (miR-30e) against heart failure (HF) in MI rats. METHODS: First, the differentially expressed miRNAs were analyzed using a miRNA-based microarray of MI. Subsequently, we overexpressed miR-30e in rat BMMSCs to isolate exosomes. A rat model with MI was developed and treated with Exo. Next, we examined the cardiac function of the rats, followed by the myocardial tissue extraction. HE, TUNEL and Masson's staining were used to assess the protective effects of exosomes against HF in rats. Subsequently, H9C2 cells exposed to OGD were further co-cultured with Exo. We used bioinformatics to predict the target mRNA of miR-30e and verified the binding relationship. Finally, we tested the expression and role of NF-κB p65/Caspase-9 signaling in myocardial tissues and cells. RESULTS:miR-30e was poorly expressed in myocardial tissues of MI rats. Moreover, treatment of rats with Exo overexpressing miR-30e ameliorated pathological damage, cardiomyocyte apoptosis, and fibrosis in rat myocardial tissues. Furthermore, miR-30e negatively regulated LOX1 expression, which was overexpressed in the MI rats, but further Exo treatment inhibited LOX1 expression. Moreover, Exo overexpressing miR-30e impaired the NF-κB p65/Caspase-9 signaling in myocardial tissues of MI rats. The NF-κB p65/Caspase-9 signaling inhibitor repressed the apoptosis and fibrosis of cardiomyocytes as well. CONCLUSION: Exosomal miR-30e from rat BMMSCs markedly inhibited LOX1 expression, thereby downregulating the activity of the NF-κB p65/Caspase-9 signaling and ameliorating HF after MI in rats. AJTR
Authors: Rudy F Duisters; Anke J Tijsen; Blanche Schroen; Joost J Leenders; Viola Lentink; Ingeborg van der Made; Veronica Herias; Rick E van Leeuwen; Mark W Schellings; Paul Barenbrug; Jos G Maessen; Stephane Heymans; Yigal M Pinto; Esther E Creemers Journal: Circ Res Date: 2008-12-18 Impact factor: 17.367