Background Adipose tissue-derived adipokines are involved in various crosstalk between adipose tissue and other organs. Omentin1, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin1 in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated. Methods The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin1 were constructed by a fat-specific adeno-associated virus (AAV) vector system. Results We demonstrated that circulating omentin1 level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin1 ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin1 increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin1 strengthened OGD-injured cardiomyocyte viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin1 also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin1 on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics and mitophagy. Conclusion Omentin1 improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin1 in cardiovascular diseases from the perspective of crosstalk between heart and adipose tissue.
Background Adipose tissue-derived adipokines are involved in various cross-talk between adipose tissue and other organs. Omentin, a novel adipokine, exerts vital roles in the maintenance of body metabolism, insulin resistance and the like. However, the protective effect of omentin in myocardial ischemia (MI)-induced heart failure (HF) and its specific mechanism remains unclear and to be elucidated. Methods The model of MI-induced HF mice and oxygen glucose deprivation (OGD)-injured cardiomyocytes were performed. Mice with overexpression of omentin were constructed by a fat-specific adeno-associated virus (AAV) vector system. Results We demonstrated that circulating omentin level diminished in HF patients compared with healthy subjects. Furthermore, the fat-specific overexpression of omentin ameliorated cardiac function, cardiac hypertrophy, infarct size and cardiac pathological features, and also enhanced SIRT3/FOXO3a signaling in HF mice. Additionally, administration with AAV-omentin increased mitochondrial fusion and decreased mitochondrial fission in HF mice, as evidenced by up-regulated expression of Mfn2 and OPA1, and downregulation of p-Drp1(Ser616). Then, it also promoted PINK1/Parkin-dependent mitophagy. Simultaneously, treatment with recombinant omentin strengthened OGD-injured cardiomyocytes viability, restrained LDH release, and enhanced the mitochondrial accumulation of SIRT3 and nucleus transduction of FOXO3a. Besides, omentin also ameliorated unbalanced mitochondrial fusion-fission dynamics and activated mitophagy, thereby, improving the damaged mitochondria morphology and controlling mitochondrial quality in OGD-injured cardiomyocytes. Interestingly, SIRT3 played an important role in the improvement effects of omentin on mitochondrial function, unbalanced mitochondrial fusion-fission dynamics, and mitophagy. Conclusion omentin improves MI-induced HF and myocardial injury by maintaining mitochondrial dynamical homeostasis and activating mitophagy via upregulation of SIRT3/FOXO3a signaling. This study provides evidence for further application of omentin in cardiovascular diseases from the perspective of cross-talk between heart and adipose tissue.
PurposeQiShenYiQi dripping pill (QSYQ) is a traditional Chinese medicine for alleviating cardiovascular diseases. Whereas, the potential mechanism remains to be further elucidated. Thus, this paper is designed to explore the protective mechanism of QSYQ in myocardial ischemia (MI)-induced injury.MethodsMyocardial ischemia was induced in mice by left anterior descending coronary artery ligation (CAL). Then, mice were treated by QSYQ dripping pills (12, 35 and 105 mg/kg) for 14 days. The effect and mechanism of QSYQ against MI injury were investigated in vivo.ResultsTreatment with QSYQ significantly improved the contractile function, and extenuated myocardial fibrosis and inflammatory cell infiltration after MI injury. QSYQ administration also reduced the level of LDH and NT-pro BNP in serum. Additionally, myocardial iron content and serum MDA, 4-HNE were decreased and GSH was increased after QSYQ administration. The mRNA expression of GPX4 and SLC7A11 were increased, and PTGS2 mRNA expression level was reduced by QSYQ treatment. Moreover, QSYQ ameliorated myocardial mitochondrial ultrastructure damage and decreased mitochondrial ROS production. Furthermore, QSYQ heightened the expressions of PGC-1α, TFAM and Nrf1, which indicated that QSYQ could promote mitochondrial biogenesis. In addition, QSYQ treatment also increased MFN2 and OPA1 expressions, while the expression of p-DRP1 was decreased.ConclusionsAll these suggested that QSYQ could promote mitochondrial dynamic homeostasis to improve myocardial injury. QSYQ could alleviate MI-induced ferroptosis via improving mitochondrial dynamical homeostasis and biogenesis, which provided references for its clinical application.
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