Autophagy is a complex ''self-eating'' process and could be utilized for cell survival under stresses. Statins, which could reduce apoptosis in mesenchymal stem cells (MSCs) during both ischemia and hypoxia/serum deprivation (H/SD), have been proved to induce autophagy in some cell lines. We have previously shown that atorvastatin (ATV) could regulate AMP-activated protein kinase (AMPK), a positive modulator of autophagy, in MSCs. Thus, we hypothesized that autophagy activation through AMPK and its downstream molecule mammalian target of rapamycin (mTOR) may be a novel mechanism of ATV to protect MSCs from apoptosis during H/SD. Here, we demonstrated that H/SD induced autophagy in MSCs significantly as identified by increasing acidic vesicular organelle-positive cells, type II of light chain 3 (LC3-II) expression, and autophagosome formation. The levels of H/SD-induced apoptosis were increased by autophagy inhibitor 3-methyladenine (3-MA) while decreased by rapamycin, an autophagic inducer. ATV further enhanced the autophagic activity observed in MSCs exposed to H/SD. Treatment with 3-MA attenuated ATV-induced autophagy and abrogated the protective effects of ATV on MSC apoptosis, while rapamycin failed to cause additional effects on either autophagy or apoptosis compared with ATV alone. The phosphorylation of AMPK was upregulated whereas the phosphorylation of mTOR was downregulated in ATV-treated MSCs, which were both attenuated by AMPK inhibitor compound C. Further, treatment with compound C reduced the ATV-induced autophagy in MSCs under H/SD. These data suggest that autophagy plays a protective role in H/SD-induced apoptosis of MSCs, and ATV could effectively activate autophagy via AMPK/mTOR pathway to enhance MSC survival during H/SD.

Acute myocardial infarction (AMI) is one of the leading causes of mortality around the world, and the inflammatory response plays a pivotal role in the progress of myocardial necrosis and ventricular remodeling, dysfunction and heart failure after AMI. Therapies aimed at modulating immune response after AMI on a molecular and cellular basis are urgently needed. Exosomes are a type of extracellular vesicles which contain a large amount of biologically active substances, like lipids, nucleic acids, proteins and so on. Emerging evidence suggests key roles of exosomes in immune regulation post AMI. A variety of immune cells participate in the immunomodulation after AMI, working together to clean up necrotic tissue and repair damaged myocardium. Stem cell therapy for myocardial infarction has long been a research hotspot during the last two decades and exosomes secreted by stem cells are important active substances and have similar therapeutic effects of immunomodulation, anti-apoptosis, anti-fibrotic and angiogenesis to those of stem cells themselves. Therefore, in this review, we focus on the characteristics and roles of exosomes produced by both of endogenous immune cells and exogenous stem cells in myocardial repair through immunomodulation after AMI.

Although exosomes were previously recognized as a mechanism for discharging useless cellular components, growing evidence has elucidated their roles in conveying information between cells. They contribute to cell–cell communication by carrying nucleic acids, proteins and lipids that can, in turn, regulate behavior of the target cells. Recent research suggested that exosomes extensively participate in progression of diverse cardiovascular diseases (CVDs), such as myocardial infarction, cardiomyopathy, pulmonary arterial hypertension and others. Here, we summarize effects of exosome-derived molecules (mainly microRNAs and proteins) on cardiac function, to examine their potential applications as biomarkers or therapeutics in CVDs.

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BackgroundThe incidence, clinical outcomes and antithrombotic treatment spectrum of atrial fibrillation (AF) in patients hospitalized with acute myocardial infarction (AMI) have not been well studied in Chinese population.MethodsTwenty-six thousand five hundred ninety-two consecutive patients diagnosed with AMI were enrolled in CAMI registry from January 2013 to September 2014. After excluding 343 patients with uncertain AF status and 1,591 patients transferred out during hospitalization, 24,658 patients were finally included in this study and involved in analysis.ResultsIn the CAMI registry, 740 (3.0%) patients were recorded with AF prevalence during hospitalization. Higher-risk baseline clinical profile was observed in patients with AF. These patients were less likely to receive reperfusion/revascularization than those without AF. The in-hospital mortality (including death and treatment withdrawal) was significantly higher in patients with AF than that of without AF (25.2% vs. 7.2%, respectively; p < 0.01). The case of composite of adverse events was similar, which included death, treatment withdrawal, re-infarction, heart failure or stroke (42.1% vs. 16.0%, p <0.01). In multivariate logistic regression analysis, AF was an independent predictor for in-hospital mortality (odds ratio, 1.88; 95% confidence interval: 1.27–2.78) and the composite of adverse events (odds ratio, 2.11; 95% CI: 1.63–2.72). Only 5.1% of patients with AF were treated with warfarin, and 1.7% were treated with both warfarin and dual antiplatelet therapy.ConclusionsThe analysis was based on the CAMI registry in China. The patients hospitalized for AMI who developed AF were at significantly higher risk for in-hospital mortality and other adverse events. However, the anticoagulants including warfarin have been largely underused post hospital discharge.Trial registrationClinical Trial Registration: Identifier: NCT01874691.

Cardiac fibrosis, a common pathophysiologic process in most heart diseases, refers to an excess of extracellular matrix (ECM) deposition by cardiac fibroblasts (CFs), which can lead to cardiac dysfunction and heart failure subsequently. Not only CFs but also several other cell types including macrophages and endothelial cells participate in the process of cardiac fibrosis via different molecular pathways. Exosomes, ranging in 30–150 nm of size, have been confirmed to play an essential role in cellular communications by their bioactive contents, which are currently a hot area to explore pathobiology and therapeutic strategy in multiple pathophysiologic processes including cardiac fibrosis. Cardioprotective factors such as RNAs and proteins packaged in exosomes make them an excellent cell-free system to improve cardiac function without significant immune response. Emerging evidence indicates that targeting selective molecules in cell-derived exosomes could be appealing therapeutic treatments in cardiac fibrosis. In this review, we summarize the current understandings of cellular effectors, molecular pathways, and exosomal roles in cardiac fibrosis.

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