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Atrial fibrillation (AF) is one of the most prevalent arrhythmias. Myocardial sleeves of the pulmonary vein are critical in the occurrence of AF. Our study aims to investigate the effect of synthetic vascular smooth muscle cells (SMCs) on gap junction proteins in cardiomyocytes. (1) Extraction of vascular SMCs from the pulmonary veins of Norway rats. TGF-β1 was used to induce the vascular SMCs switching to the synthetic phenotype and 18-α-GA was used to inhibit gap junctions of SMCs. The contractile and synthetic phenotype vascular SMCs were cocultured with HL-1 cells; (2) Western blotting was used to detect the expression of Cx43, Cx40 and Cx45 in HL-1 cells, and RT-PCR to test microRNA 27b in vascular SMCs or in HL-1 cells; (3) Lucifer yellow dye transfer experiment was used to detect the function of gap junctions. (1) TGF- β1 induced the vascular SMCs switching to synthetic phenotype; (2) Cx43 was significantly increased, and Cx40 and Cx45 were decreased in HL-1 cocultured with synthetic SMCs; (3) The fluorescence intensity of Lucifer yellow was higher in HL-1 cocultured with synthetic SMCs than that in the cells cocultured with contractile SMCs, which was inhibited by18-α-GA; (4) the expression of microRNA 27b was increased in HL-1 cocultured with synthetic SMCs, which was attenuated markedly by 18-α-GA. (5) the expression of ZFHX3 was decreased in HL-1 cocultured with synthetic SMCs, which was reversed by 18-α-GA. The gap junction proteins of HL-1 were regulated by pulmonary venous SMCs undergoing phenotypic transition in this study, accompanied with the up-regulation of microRNA 27b and the down-regulation of ZFHX3 in HL-1 cells, which was associated with heterocellular gap junctions between HL-1 and pulmonary venous SMCs.

Acute brain reperfusion stress is associated with mitochondrial dysfunction through unknown mechanisms. Accordingly, there is no effective drug to control the development and progression of brain reperfusion stress currently. The aim of our investigation is to verify whether melatonin attenuates acute brain reperfusion stress via affecting mitochondrial function. Our studies demonstrated that melatonin treatment suppressed reperfusion-induced neuron death. At the molecular levels, melatonin treatment modulated mitochondrial homeostasis via activating mitochondrial fusion. At the stage of reperfusion, MFN2 expression was downregulated, contributing to mitochondrial fusion inhibition. Interestingly, MFN2-related mitochondrial fusion was reversed by melatonin. Loss of MFN2-related mitochondrial fusion abrogated the protective actions of melatonin on mitochondrial function. Mechanistically, melatonin sustained MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway. Overexpression of Mst1 attenuated the beneficial effects of melatonin on mitochondrial fusion, evoking mitochondrial damage and neuron death in the setting of brain reperfusion stress. Taken together, our results confirmed the protective effects of melatonin on acute brain reperfusion stress. Melatonin treatment activated MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway, finally sustaining mitochondrial function and reducing reperfusion-mediated cerebral injury.

Acute brain reperfusion stress is associated with mitochondrial dysfunction through unknown mechanisms. Accordingly, there is no effective drug to control the development and progression of brain reperfusion stress currently. The aim of our investigation is to verify whether melatonin attenuates acute brain reperfusion stress via affecting mitochondrial function. Our studies demonstrated that melatonin treatment suppressed reperfusion-induced neuron death. At the molecular levels, melatonin treatment modulated mitochondrial homeostasis via activating mitochondrial fusion. At the stage of reperfusion, MFN2 expression was downregulated, contributing to mitochondrial fusion inhibition. Interestingly, MFN2-related mitochondrial fusion was reversed by melatonin. Loss of MFN2-related mitochondrial fusion abrogated the protective actions of melatonin on mitochondrial function. Mechanistically, melatonin sustained MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway. Overexpression of Mst1 attenuated the beneficial effects of melatonin on mitochondrial fusion, evoking mitochondrial damage and neuron death in the setting of brain reperfusion stress. Taken together, our results confirmed the protective effects of melatonin on acute brain reperfusion stress. Melatonin treatment activated MFN2-related mitochondrial fusion via suppressing Mst1-Hippo pathway, finally sustaining mitochondrial function and reducing reperfusion-mediated cerebral injury.