Vitexin Mitigates Myocardial Ischemia/Reperfusion Injury in Rats by Regulating Mitochondrial Dysfunction via Epac1-Rap1 Signaling
| Autor: | Yuqian Sun, Shuo Chen, Binshan Zha, Bohan Xu, Huaqin Zhu, Caijuan Ding, Huanhua Yang, Wei Xue, Junyan Zhang, Liuyi Dong, Cheng Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Agonist Aging Article Subject medicine.drug_class Myocardial Ischemia MFN2 Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Pharmacology Biochemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Guanine Nucleotide Exchange Factors Myocardial infarction Apigenin chemistry.chemical_classification Reactive oxygen species QH573-671 business.industry Cell Biology General Medicine Hypoxia (medical) medicine.disease Rats 030104 developmental biology chemistry Apoptosis medicine.symptom business Cytology Reperfusion injury Signal Transduction Research Article |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2021 (2021) Oxidative Medicine and Cellular Longevity |
| ISSN: | 1942-0994 1942-0900 |
| Popis: | Revascularization is an effective therapy for rescuing myocardial tissue after ischemic events. However, the process of reperfusion can lead to more severe cardiomyocyte damage, called myocardial ischemia-reperfusion (I/R) injury (MIRI). We have previously shown that vitexin (VT) (a flavonoid compound derived from natural products) protects against MIRI; however, the exact mechanisms underpinning this effect require further elucidation. This study is aimed at elucidating the protective mechanism of VT in inhibiting ischemic myocardial mitochondrial dysfunction and reducing cardiomyocyte apoptosis by regulating Epac1-Rap1 signaling. Isolated rat hearts were subjected to MIRI in a Langendorff perfusion system, and H9c2 cells were subjected to hypoxia/reoxygenation (H/R) in vitro. Our analyses show that during I/R, Epac1 expression was upregulated, left ventricular dysfunction deteriorated, mitochondrial dynamics were disrupted, and both myocardial cells and tissues exhibited apoptosis. Furthermore, administration of 8-CPT (an Epac agonist) exacerbated cardiomyocyte injury and mitochondrial dysfunction. Interestingly, suppressing the function of Epac1 through VT or ESI-09 (an Epac inhibitor) treatment during I/R reduced the myocardial infarct size, cardiomyocyte apoptosis, and reactive oxygen species production; alleviated mitochondrial dysfunction by increasing mitochondrial membrane potential; elevated MFN2 expression; and inhibited Drp1 expression. To our knowledge, our results reveal, for the first time, the mechanisms underlying the protective effect of VT in the myocardium of rats with MIRI. Moreover, we provide a new target and theoretical basis for VT in the treatment of ischemic heart disease. |
| Databáze: | OpenAIRE |
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