Exosomes extracted from mesenchymal stem cells (MSCs) was reported to reduce myocardial ischemia/reperfusion damage. Besides, stromal‐derived factor 1 (SDF1a) functions as cardiac repair after myocardial infarction (MI). Therefore, the present study aims to identify whether exosomes (Exo) released from SDF1‐overexpressing MSCs display a beneficial effect on ischemic myocardial infarction. Initially, a gain‐of‐function study was performed to investigate the function of SDF1 in ischemic myocardial cells and cardiac endothelial cells. Coculture experiments were performed to measure potential exosomic transfer of SDF1 from MSCs to ischemic myocardial cells and cardiac endothelial cells. During the coculture experiments, exosome secretion was disrupted by neutral sphingomyelinase inhibitor GW4869 and upregulated exosomal SDF1 using SDF1 plasmid. Effects of Exo‐SDF1 on cardiac function in MI mice were investigated in vivo. MSCs suppressed myocardial cell apoptosis and promoted microvascular regeneration of endothelial cells through secretion of exosomes. The addition of GW4869 led to increased apoptotic capacity of myocardial cells, decreased microvascular formation ability of endothelial cells, enhanced autophagy ability, and elevated Beclin‐1 level as well as ratio of LC3II/LC3I. Overexpression of SDF1 and Exo‐SDF1 inhibited apoptosis and autophagy of myocardial cells, but promoted tube formation of endothelial cells. The interference of PI3K signaling pathway promoted apoptosis and autophagy of myocardial cells, but inhibited tube formation of endothelial cells. SDF1 activated the PI3K signaling pathway. Exo‐SDF1 protected cardiac function of MI mice and inhibited myocardial tissue damage. This study provided evidence that SDF1 overexpression in MSCs‐derived exosomes inhibited autophagy of ischemic myocardial cells and promoted microvascular production of endothelial cells.

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Objectives: Recent studies have reported increased red blood cell distribution width (RDW) has been associated with adverse outcomes in heart failure and stable coronary disease. We investigated the association between RDW and risk of all-cause mortality in patients with ST-elevation myocardial infarction (STEMI) who were free of heart failure at baseline. Methods: We enrolled 691 patients with STEMI who were free of heart failure at baseline confirmed by coronary angiography in Beijing Friendship Hospital from January 2007 to December 2008. According to the median RDW at baseline (13.0%) on admission, the patients were divided into two groups: a low-RDW group (RDW <13.0%, n = 329) and a high-RDW group (RDW ≥13.0%, n = 362). All-cause mortality rates were compared between groups. Mean duration of follow-up was 41.8 months. The relation between RDW and clinical outcomes after hospital discharge were tested using Cox regression models, adjusting for clinical variables. At the same time, the sensitivity and specificity of RDW were analyzed by ROC analysis. Results: Forty-seven patients (6.8%) died during follow-up. The cumulative incidence of all-cause death was significantly higher in the high-RDW group than in the low-RDW group (log-rank p = 0.007). Multivariate analysis revealed that high RDW was associated with all-cause mortality (hazard ratio: 3.43; 95% confidence interval: 1.17-8.32; p = 0.025). The area under the ROC curve was 0.562. Conclusion: From the statistical point of view, increased RDW is associated with all-cause and cardiac mortality rates in patients with STEMI who were free of heart failure at baseline. But RDW is a marker with a very low prognostic accuracy that does not seem to be clinically helpful.