Notoginsenoside R1 (NGR1), the primary bioactive compound found in Panax notoginseng, is believed to have antihypertrophic and antiapoptotic properties, and has long been used to prevent and treat cardiovascular diseases. However, its potential role in prevention of diabetic cardiomyopathy remains unclear. The present study aimed to investigate the mechanism of NGR1 action in high glucose-induced cell injury. H9c2 cardiomyocytes were cultured in a high-glucose medium as an in-vitro model, and apoptotic cells were visualized using TUNEL staining. Expression of Nrf2 and HO-1 was measured using Western blotting or reverse transcription-quantitative PCR (RT-qPCR). The Nrf2 small interfering (si) RNA was transfected into cardiomyocytes using Opti-MEM containing Lipofectamine® RNAiMAX. NGR1 protected H9c2 cardiomyocytes from cell death, apoptosis and hypertrophy induced by high glucose concentration. Expression of auricular natriuretic peptide and brain natriuretic peptide was remarkably reduced in NGR1-treated H9C2 cells. Western blot analysis showed that high glucose concentration markedly inhibited AMPK, Nrf2 and HO-1, and this could be reversed by NGR1 treatment. However, the cardioprotective effect of NGR1 was attenuated by compound C, which reverses Nrf2 and HO-1 expression levels, suggesting that AMPK upregulates Nrf2 and HO-1 gene expression, protein synthesis and secretion. Transfection of H9C2 cells with Nrf2 siRNA markedly reduced the cardioprotective effect of NGR1 via reduced expression of HO-1. These results indicated that NGR1 attenuated high glucose-induced cell injury via AMPK/Nrf2 signaling and its downstream target, the HO-1 pathway. We conclude that the cardioprotective effects of NGR1 result from upregulation of AMPK/Nrf2 signaling and HO-1 expression in cardiomyocytes. Our findings suggest that NGR1 treatment might provide a novel therapy for diabetic cardiomyopathy.
Pathological cardiac hypertrophy induced by aging and neurohumoral activation, such as angiotensin II (Ang II) activation, is an independent risk factor for heart failure. The muscle really interesting new gene-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx) pathway has been previously reported to be an important mechanism underlying the pathogenesis of cardiac hypertrophy. Metformin is currently the first-line blood glucose-lowering agent that can be useful for the treatment of cardiovascular diseases. However, the potential role of metformin in the modulation of MuRF1 and MAFbx in cardiomyocyte hypertrophy remains poorly understood. The present study used H9c2 cells, a cardiomyocyte cell model. The surface area of cultured rat H9c2 myoblasts was measured and the expression levels of MuRF1 and MAFbx were quantified using western blot or reverse transcription-quantitative PCR. H9c2 cells were transfected with MuRF1 and MAFbx small interfering (si) RNA. The present study revealed that Ang II treatment significantly increased the cell surface area of model cardiomyocytes. Additionally, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA and protein expression was increased following this treatment. Ang II also downregulated MuRF1 and MAFbx protein and mRNA expression. In the H9C2, treatment with metformin attenuated hypertrophic remodeling. In addition, expression of ANP and BNP was significantly reduced in metformin-treated H9C2 cells. The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II-induced cell hypertrophy, even following treatment with metformin. Taken together, data from the present study suggest that metformin can prevent cardiac hypertrophy through the MuRF1 and MAFbx pathways.
Background Hyponatremia is an independent predictor of poor prognosis, including increased mortality and readmission, in COPD patients. Identifying modifiable etiologies of hyponatremia may help reduce adverse events in patients with AECOPD. Therefore, the aim of this study was to explore the risk factors and underlying etiologies of hyponatremia in AECOPD patients. Methods A total of 586 AECOPD patients were enrolled in this multicenter cross-sectional study. Finally, 323 had normonatremia, and 90 had hyponatremia. Demographics, underlying diseases, comorbidities, symptoms, and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was used to select potential risk factors, which were substituted into binary logistic regression to identify independent risk factors. Nomogram was built to visualize and validate binary logistics regression model. Results Nine potential hyponatremia-associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that smoking status, rate of community-acquired pneumonia (CAP), anion gap (AG), erythrocyte sedimentation rate (ESR), and serum magnesium (Mg2+) were independent variables of hyponatremia in AECOPD patients. The AUC of ROC curve of nomogram was 0.756. The DCA curve revealed that the nomogram could yielded more clinical benefits if the threshold was between 10% and 52%. Conclusions Collectively, our results showed that smoking status, CAP, AG, ESR, and serum Mg2+ were independently associated with hyponatremia in AECOPD patients. Then, these findings indicate that pneumonia, metabolic acidosis, and hypomagnesemia were the underlying etiologies of hyponatremia in AECOPD patients. However, their internal connections need further exploration.
Background and Objectives With the growing incidence of acute myocardial infarction (MI), angiogenesis is vital for cardiac function post-MI. The role of bone marrow mesenchymal stem cells (BMSCs) in angiogenesis has been previously confirmed. Irisin is considered a potential vector for angiogenesis. The objective of the present study was to investigate the potential role of irisin in the angiogenesis of BMSCs. Methods and Results In vivo , irisin-treated BMSCs (BMSCs+irisin) were transplanted into an MI mouse model. On day 28 post-MI, blood vessel markers were detected, and cardiac function and infarct areas of mice were evaluated. In vitro , paracrine effects were assessed by examining tube formation in human umbilical vein endothelial cells (HUVECs) co-cultured with the BMSCs+irisin supernatant. The scratch wound-healing assay was performed to evaluate HUVEC migration. Western blotting was performed to determine PI3k/Akt pathway activation in the BMSCs+irisin group. Transplantation of BMSCs+irisin promoted greater angiogenesis, resulting in better cardiac function in the MI mouse model than in controls. In the BMSC+irisin group, HUVECs demonstrated enhanced tube formation and migration. Activation of the PI3k/Akt pathway was found to be involved in mediating the role of irisin in the angiogenesis of BMSCs. Conclusions In cardiovascular diseases such as MI, irisin administration can enhance angiogenesis of BMSCs and promote cardiac function via the PI3k/Akt pathway, optimizing the therapeutic effect based on BMSCs transplantation.
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