Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI. Methods and results EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221–3p was highly expressed in HIF-1α-EVs. After miR-221–3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated. Conclusion EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221–3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.

Objective: The purpose of this study was to prospectively investigate the correlation between CT angiographic clot load (CTACL) score, pulmonary perfusion defect (PPD) score and the global right ventricular function in the assessment of pulmonary embolism (PE) severity. Methods: 49 patients with acute PE, who underwent dual-source CT scan, were included in the study. CT angiography and perfusion imaging were performed. Data from electrocardiogram-gated coronary angiography scanning protocol were used for right ventricular function analysis. Two readers evaluated the CTACL and PPD scores using the Qanadli and Chae methods, respectively. Results: The PPD score had a strong positive correlation with the CTACL score (r50.72, p,0.001) and both scores in turn had a strong positive correlation with the right ventricular/left ventricular (RV/LV) diameter ratio (r50.60, r50.62, p,0.001). However, the PPD score had a strong negative correlation with ejection fraction (EF) (r520.63, p,0.001) while the CTACL score had a low negative correlation with EF (r520.33, p50.02). Between the RV/LV,1 group (n535) and the RV/LV .1 group (n514), the PPD score, CTACL score, pulmonary artery trunk diameter, EF and reflux of inferior vena cava were significantly different, all with p,0.001. The end-systolic volume (p50.01) was significantly different but the end-diastolic volume (p50.11) and stroke volume (p50.08) showed no statistically significant difference between the two groups. Conclusion: Therefore, considering PPD scores, CTACL scores and cardiovascular manifestations together may be helpful in the evaluation of PE severity. Pulmonary CT angiography (CTA) has been established as the first-line imaging technique for the diagnosis of pulmonary embolism (PE) in daily clinical practice [1,2]. Routine CT pulmonary angiography not only provides pulmonary arterial clot load information, but may even help to diagnose alternative causes for the patient's symptoms, such as pneumothorax, pneumonia, pulmonary oedema or pleural effusion. However, it only provides anatomical and morphological images and no information regarding perfusion function. In acute PE patients, anatomical obstruction is the most important cause of compromised physiology, and the release of vasoactive and bronchoactive agents from platelets may lead to deleterious ventilation-perfusion mismatch [3]. Therefore, assessment of both anatomical obstruction and functional perfusion is important. The emergence of dual-source CT means that simultaneous evaluation of lung parenchyma perfusion and vascular blockage is now feasible. It has been shown to be a reliable method, with only one CT scan, in animal experiments [4] and clinical practice [5][6][7]. Besides lung parenchyma perfusion and arterial obstruction, right ventricular function is also an important tool for assessment of severity and is a predictor of mortality [8,9] in acute PE patients. Several studies [10][11][12][13] have shown that the global right ventricular function can be accurately assessed with electrocardio...

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