Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been demonstrated as an ideal autologous stem cells source for cell-based therapy for myocardial infarction (MI). However, poor viability of donor stem cells after transplantation limits their therapeutic efficiency, whereas the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for maintaining homeostasis and normal function. Here, we investigated the potential role of autophagy on apoptosis in BM-MSCs induced by hypoxic injury. BM-MSCs, isolated from male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury for 6, 12, and 24 h, respectively. The autophagy state was regulated by 3-methyladenine (3MA) and rapamycin administration. Furthermore, compound C was administrated to inhibit AMPK. The apoptosis induced by H/SD was determined by TUNEL assays. Meanwhile, autophagy was measured by GFP-LC3 plasmids transfection and transmission electron microscope. Moreover, protein expressions were evaluated by Western blot assay. In the present study, we found that hypoxic stress increased autophagy and apoptosis in BM-MSCs time dependently. Meanwhile, hypoxia increased the activity of AMPK/mTOR signal pathway. Moreover, increased apoptosis in BM-MSCs under hypoxia was abolished by 3-MA, whereas was aggravated by rapamycin. Furthermore, the increased autophagy and apoptosis in BM-MSCs induced by hypoxia were abolished by AMPK inhibitor compound C. These data provide evidence that hypoxia induced AMPK/mTOR signal pathway activation which regulated the apoptosis and autophagy in BM-MSCs. Furthermore, the apoptosis of BM-MSCs under hypoxic condition was regulated by autophagy via AMPK/mTOR pathway.

Nebivolol, third-generation β-blocker, may activate β3-adrenergic receptor (AR), which has been emerged as a novel and potential therapeutic targets for cardiovascular diseases. However, it is not known whether nebivolol administration plays a cardioprotective effect against myocardial infarction (MI) injury. Therefore, the present study was designed to clarify the effects of nebivolol on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Nebivolol, β3-AR antagonist (SR59230A), Nitro-L-arginine methylester (L-NAME) or vehicle was administered for 4 weeks after MI operation. Cardiac function was monitored by echocardiography. Moreover, the fibrosis and the apoptosis of myocardium were assessed by Masson's trichrome stain and TUNEL assay respectively 4 weeks after MI. Nebivolol administration reduced scar area by 68% compared with MI group (p<0.05). Meanwhile, nebivolol also decreased the myocardial apoptosis and improved the heart function after MI (p<0.05 vs. MI). These effects were associated with increased β3-AR expression. Moreover, nebivolol treatment significantly increased the phosphorylation of endothelial NOS (eNOS) and the expression of neuronal NOS (nNOS). Conversely, the cardiac protective effects of nebivolol were abolished by SR and L-NAME. These results indicate that nebivolol protects against MI injury. Furthermore, the cardioprotective effects of nebivolol may be mediated by β3-AR-eNOS/nNOS pathway.

Aims: Several recent reports have shown irisin protects the heart against ischemia/ reperfusion injury. However, the effect of irisin on I/R injury in diabetic mice has not been described. The present study was designed to investigate the role of irisin in myocardial ischemia-reperfusion (MI/R) injury in diabetic mice. Methods: A mouse model of diabetes was established by feeding wild type or genemanipulated adult male mice with a high-fat diet. All the mice received intraperitoneal injection of irisin or PBS. Thirty minutes after injection, mice were subjected to 30 min of myocardial ischemia followed by 3h (for cell apoptosis and protein determination), 24 h (for infarct size and cardiac function). Results: Knockout of gene FNDC5 augmented MI/R injury in diabetic mice, while irisin treatment attenuated MI/R injury, improved cardiac function, cellular ATP biogenetics, mitochondria potential, and impaired mitochondrion-related cell death. More severely impaired AMPK pathway was observed in diabetic FNDC5-/mice received MI/R. Knockout of gene AMPK blocks the beneficial effects of irisin on MI/R injury, cardiac function, cellular ATP biogenetics, mitochondria potential, and mitochondrion-related cell death. Conclusions: Our present study demonstrated that irisin improves the mitochondria function and attenuates MI/R injury in diabetic mice through AMPK pathway.

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them had been confirmed as coronary disease by coronary angiography. At this sampling 46 RA patients were developed MI. The control group includes 60 subjects who were free of MI. The characteristics of both groups were compared including demographics, traditional cardiovascular risks and laboratory findings. Cases of MI and controls were compared by disease activity variables and risk factors using the student's t test (for continuous variables) or the c 2 test (for dichotomous variables). Variables that had a P value of <0.2 in the single factor logistic regression were entered into a multivariate model. Results: There were no significant differences about demographics, traditional cardiovascular between MI group and control group, such as age, gender, Body Mass Index (BMI), the percentage of hypertension (HT), diabetes mellitus (DM), hyperlipidaemia (HLP) and Smoking. MI group showed increased Erythrocyte Sedimentation Rate (ESR) (P¼0.014),C-reactive protein (CRP) (P¼0.000) and creatinine (P¼0.024) levels than control group. The result of univariate logistic's regression demonstrated that ESR (P¼0.009), CRP (P¼0.022), CR (P¼0.030), lipoproteins (LPa) (P¼0.097) and high-sensitivity C-reactive protein (Hs-CRP) (P¼0.009) are associated with increased risk of MI in RA. The result of analysis of multivariate logistic's regression showed that ESR [OR 95% CI 1.024 (1.007-1.043), P¼0.007] was an independent risk factor of MI in RA patients. Conclusions: Patients with RA who developed MI had similar traditional cardiovascular risk factors compared to RA patients without MI, but had significant differences in inflammatory indexes. Inflammation may accelerate atherogenesis and have an excess risk of MI in RA patient with cardiovascular disease.Objectives: Nebivolol, third-generation b-blocker, may activate b3-adrenergic receptor (AR), which has been emerged as a novel and potential therapeutic targets for cardiovascular diseases. However, it is not known whether nebivolol administration plays a cardioprotective effect against myocardial infarction (MI) injury. Therefore, the present study was designed to clarify the effects of nebivolol on MI injury and to elucidate the underlying mechanism. Methods: MI model was constructed by left anterior descending (LAD) artery ligation. Nebivolol, SR59230A (SR), Nitro-L-arginine methylester (L-NAME) or vehicle was administered one day after MI operation. Cardiac function was monitored by echocardiography. Moreover, the fibrosis and the apoptosis of myocardium were assessed by Masson's trichrome stain and TUNEL assay respectively. Results: Nebivolol administration reduced scar area by 68% compared with MI group (P<0.05). Meanwhile, nebivolol also decreased the myocardial apoptosis and improved the heart function after MI (P<0.05 vs. MI). These effects were associated with increased b3-AR expression. Furthermore, nebivolol treatment significantly increased the phosphorylation of endothelial NOS (eNOS) and the expression of neuronal NOS (nNOS). Conversely, the cardiac protective effect...