Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

Coronary artery disease (CAD) represents a fatal public threat. The involvement of extracellular vesicles (EVs) in CAD has been documented. This study explored the regulation of embryonic stem cells (ESCs)-derived EVs-hnRNPU-actin complex in human coronary artery endothelial cell (HCAEC) growth. Firstly, in vitro HCAEC hypoxia models were established. EVs were extracted from ESCs by ultracentrifugation. HCAECs were treated with EVs and si-VEGF for 24 h under hypoxia, followed by assessment of cell proliferation, apoptosis, migration, and tube formation. Uptake of EVs by HCAECs was testified. Additionally, hnRNPU, VEGF, and RNA Pol II levels were determined using Western blotting and CHIP assays. Interaction between hnRNPU and actin was evaluated by Co-immunoprecipitation assay. HCAEC viability and proliferation were lowered, apoptosis was enhanced, wound fusion was decreased, and the number of tubular capillary structures was reduced under hypoxia, whereas ESC-EVs treatment counteracted these effects. Moreover, EVs transferred hnRNPU into HCAECs. EVs-hnRNPU-actin complex increased RNA Pol II level on the VEGF gene promoter and promoted VEGF expression in HCAECs. Inhibition of hnRNPU or VEGF both annulled the promotion of EVs on HCAEC growth. Collectively, ESC-EVs-hnRNPU-actin increased RNA Pol II phosphorylation and VEGF expression, thus promoting HCAEC growth.</p

Table_1_The Association Between Recurrence of Atrial Fibrillation and Revascularization in Patients With Coronary Artery Disease After Catheter Ablation.XLSX

Aim: The connection between revascularization for coronary artery disease (CAD) and the incidence of recurrent events of atrial fibrillation (AF) after ablation is unclear. This study aimed to explore the relationship between coronary revascularization and AF recurrence in patients who underwent radiofrequency catheter ablation (RFCA).Methods: Four hundred and nineteen patients who underwent performed coronary angiography at the same time as RFCA were enrolled in this study. Obstructive CAD was defined as at least one coronary artery vessel stenosis of ≥75% and percutaneous coronary intervention (PCI) was recommended. Non-obstructive CAD was defined as coronary artery vessel stenosis of Results: In total, 102, 95, and 212 patients were undergone coronary angiography and diagnosed as having obstructive CAD, Non-obstructive CAD, and Non-CAD, respectively. During the 24-month follow-up period, patients without obstructive CAD were significantly more likely to achieve freedom from AF than patients with obstructive CAD (hazard ratio [HR]: 1.72; 95% confidence interval [CI]: 1.23–2.41; P = 0.001). The recurrence rate of AF was significantly lower in patients who underwent PCI than in those who did not (HR: 0.45; 95% CI: 0.25–0.80; P = 0.007). The multivariate regression analysis showed that the other predictors of AF recurrence for obstructive CAD were multivessel stenosis (HR: 1.92; 95% CI: 1.04–3.54; P = 0.036) and left atrial diameter (HR: 2.56; 95% CI: 1.31–5.00; P = 0.006).Conclusions: This study suggests that obstructive CAD is associated with a higher rate of AF recurrence. Additionally, For patients with CAD, coronary revascularization is related to a lower recurrence rate of AF after RFCA.</p

Additional file 1: of S1PR2 antagonist ameliorate high glucose-induced fission and dysfunction of mitochondria in HRGECs via regulating ROCK1

Figure S1. Mitochondrial morphology and physiological functions in HRGECs treated with normal glucose (NG, 5.5 mM), high glucose (HG, 30mM), or mannitol (Mnt, 30mM) as an osmotic glucose (NG, 5.5 mM), high glucose (HG, 30mM), or mannitol (Mnt, 30mM) as an osmotic control for 72 h. (A) Mitochondrial morphology changes were observed under an electron microscopy. (B) ATP production was measured using a commercial ATPlite assay kit and quantified by reading luminescence on a microplate reader. (C) Total intracellular ROS generation was assessed by using the fluorogenic probe DCF-DA and observed under a fluorescent microscope, and further quantified with flow cytometric assay. (D) Ca2+ levels in mitochondria were determined by using the Ca2+ probe Rhod-2 AM and imaged with a fluorescent microscope, and quantified with flow cytometry. Data were normalized with the values of the NG-treated cells set as 100% or 1. Results are expressed as mean Âą SD of three independent experiments. *P < 0.05 versus the NG group; #P < 0.05 versus the Mnt group. Figure S2. S1PR2 antagonist reverses HG-induced endothelial cell dysfunction. HEGECs were pretreated with JTE-013, a S1PR2 inhibitor, for 30 min and then incubated with normal glucose (NG) or high glucose (HG) for 72 h. (A) The cell permeability was measured the FITC-BSA that crossed the monolayer, and quantified by fluorescence plate reader. (B) HRGECs were stained with both Annexin V and propidium iodide (PI), then determined using flow cytometric analysis. (C) The degree of migration of different groups was quantified by microscope. Results are expressed as mean Âą SD of three independent experiments. *P < 0.05 versus the HG group; #P <0.05 versus the NG group. (DOCX 9720 kb