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BACKGROUND Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary circulatory resistance. Pulmonary vascular endothelial dysfunction is one of the main causes of primary PAH. Endothelial progenitor cells (EPCs) can proliferate and differentiate into vascular endothelial cells and play an important role in maintaining normal endothelial function. Mineralocorticoid receptor inhibitor has been reported to be used in the treatment of PAH. However, the role and the underlying mechanism of aldosterone (ALDO) in PAH remains unclear. MATERIAL AND METHODS Rats were divided to 4 groups (n=10 per group) and treated with 0.9% normal saline, monocrotaline (MCT), spironolactone (SP), or MCT combined with SP. After the rats were sacrificed with an overdose of pentobarbital sodium, hematoxylin and eosin staining was performed to observe the pulmonary artery pathology section. Sirtuin 1 (SIRT1), p53, and p21 protein expression was detect by western blot. Immunofluorescence staining was performed to verify EPCs. EPCs were treated with different concentrations of ALDO. MTT assay and senescence-associated ß-galactosidase staining were used to measure cell viability and senescence. RESULTS MCT increased the vascular arterial wall thickness and wall area, inhibited SIRT1 protein expression and increased p53 and p21 protein expression in the lung tissue of rats, while SP partially reversed this effect. In addition, ALDO inhibited EPCs viability and induced senescence. The expression of p53 and p21 proteins in the EPCs were upregulated and the senescence was accelerated when EPCs were transfected with SIRT1 siRNA. CONCLUSIONS ALDO promoted EPCs senescence and inhibited EPCs proliferation by downregulating SIRT1, which regulates the p53/p21 pathway, thus promoting PAH.

BACKGROUND Endothelial injury is the early pathological change of cerebral aneurysm (CA) formation. In addition to its lipid-lowering activity, atorvastatin (ATR) also reportedly promotes vascular repair via mobilizing endothelial progenitor cells (EPC). Here, we investigated the influence of ATR on vascular worsening after CA induction in rats. MATERIAL AND METHODS Adult male Sprague-Dawley rats were randomly assigned to 3 groups: a control (CTR) group, a CA group, and a CA+ATR treatment group. Circulating EPC level and hematological and lipid profiles were measured 3 months after CA induction. Verhoeff-Van Gieson staining and transmission electron microscopy were performed to assess pathological changes in the artery wall. RT-PCR was also performed to evaluate the expression of inflammation-related genes in the aneurysmal wall. RESULTS ATR significantly restored the impaired level of circulating EPC without changing hematological and lipid profiles 3 months after CA induction. ATR markedly inhibited endothelial injury, media thinning, and CA enlargement, accompanied by reduced vascular inflammation. CONCLUSIONS Our preliminary results demonstrate that the mobilization of EPC and improvement of endothelial function by ATR contribute to the prevention of cerebral aneurysm. Further studies are warranted to investigate the detailed mechanism.

BACKGROUND The aim of this study was to investigate the effects of puerarin on vascular endothelial function and inflammatory factors in coronary artery disease (CAD) patients with stable angina pectoris (SAP). MATERIAL AND METHODS To evaluate the effects of angina pectoris, the differences of scores of the Seattle angina questionnaire (SAQ), vascular endothelial function [endothelial progenitor cells (EPCs), nitric oxide (NO) and endothelin 1 (ET-1)], and inflammatory factors [tumor necrosis factor a (TNF-α), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6)] in 2 groups were assessed before and after treatment. RESULTS Regarding the curative effect of angina pectoris, the total effective rate of the treatment group was significantly superior to that of the control group (89% vs. 65%, P<0.05). The duration of angina pectoris, the number of abnormal leads, the improvement of the ST segment depression of electrocardiogram, and the scores of SAQ life quality indexes in the treatment group were better than those of the control group (P<0.05). In the 2 groups, EPCs and NO were both elevated, while ET-1 was decreased, and the improvements of the treatment group were superior to those of the control group (P<0.05). After treatment, the average levels of serum TNF-α, hs-CRP and IL-6 in the 2 groups were all decreased, which the treatment group showed a much sharper decrease than in the control group (P<0.05). CONCLUSIONS Puerarin effectively improves clinical symptoms and vascular endothelial function and reduces the levels of inflammatory factors in patients with CAD.

BACKGROUND Endothelial progenitor cells (EPCs) were found to be a potential therapeutic choice for low extremity deep vein thrombosis. The aim of our research was to investigate the effect of resveratrol (RSV) on EPCs that may promote thrombus resolution and its potential pathway. MATERIAL AND METHODS EPCs were pretreated with RSV and migration; angiogenesis were evaluated ex vivo. Expression of miR-138 and focal adhesion kinase (FAK) was also tested. A murine model of venous thrombosis was developed as an in vivo model. The effects of RSV treatment on mice with inferior venous thrombosis were evaluated. RESULTS We found that RSV increased EPCs migration and tube formation ex vivo. RSV significantly inhibited miR-138 expression. Moreover, we demonstrated that FAK was a target of miR-138 and revealed that FAK knockdown downregulated migration and angiogenesis of RSV-treated EPCs. In addition, RSV-induced EPCs promoted thrombus resolution in a murine model of venous thrombosis. CONCLUSIONS We found the first evidence that intravenous injection of RSV-treated EPCs enhanced thrombus resolution in vivo. RSV exerted its role by reducing miR-138 expression and therefore upregulated FAK.

BACKGROUND Hypoxic preconditioning may be a key influence on functions of endothelial progenitor cells (EPCs). MATERIAL AND METHODS To investigate the role and mechanism of the Notch-Jagged1 pathway on endothelial progenitor cells in hypoxic preconditioning, endothelial progenitor cells were randomly allocated into 5 groups: 1 Normoxic control group; 2 Hypoxic blank group; 3 Hypoxic+25 μM DAPT group; 4 Hypoxic+50 μM DAPT group; 5 Hypoxic+100 μM DAPT group. After reoxygenation, protein and mRNA levels of Jagged1 were measured by Western blot and quantitative RT-PCR. The MTT test was used to assess proliferation. ELISA was used to measure NO and VEGF secretion. RESULTS Hypoxic preconditioning treatment significantly upregulated both protein and mRNA levels of Jagged1 in endothelial progenitor cells. It also enhanced proliferation ability and elevated secretion of NO and VEGF. Furthermore, after blocking the Notch pathway by using DAPT, Jagged1 expression and EP proliferation, migration, and secretion of NO and VEGF were decreased in a dose-dependent manner. CONCLUSIONS Our results suggest the Notch-Jagged1 pathway enhances EPCs proliferation and secretion ability during hypoxic preconditioning.

BACKGROUND We investigated whether microRNA-206 (miR-206) is abnormally expressed in patients with coronary artery disease (CAD). The potential mechanism by which miR-206 may regulate CAD progression was also studied. MATERIAL AND METHODS A total of 78 CAD patients in the case group and 65 subjects in the control group were enrolled in this study so that the correlation between miR-206 and CAD could be accurately determined. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were detected using a biochemistry analyzer. MiR-206 and vascular endothelial growth factor (VEGF) expression levels were tested using either reverse transcription polymerase chain reaction or western blot. Associations between miR-206 expression and different clinicopathological features of CAD patients were also analyzed. CAD cells were transfected with miR-206 mimic (miR-206), its negative control (miR-NC), miR-206 inhibitor (anti-miR-206), and its negative control (anti-miR-NC), respectively. Flow cytometry was conducted to explore the function of miR-206 in CAD cell apoptosis after transfection. Moreover, transwell assay was carried out to study the migratory ability of endothelial progenitor cells (EPCs) in CAD patients. RESULTS MiR-206 expression was enriched in both diseased EPCs and plasma of CAD patients. No significant correlation was found between decrease in miR-206 expression and different clinicopathological features. In addition, miR-206 significantly suppressed the viability and invasion of EPCs in CAD patients, and it promoted the apoptosis of their EPCs. Moreover, we found that miR-206 is able to inhibit VEGF expression. CONCLUSIONS As suggested by our study, MiR-206 can be a novel benign biomarker for CAD because it may regulate VEGF expression.

Background: Olmesartan is a type of angiotensin II receptor inhibitor that can reduce the incidence of cardiovascular events. However, its role in the function of endothelial progenitor cells in atherosclerosis patients is still unclear. Our study aimed to explore the effects and mechanism of olmesartan on endothelial progenitor cell mobilization and function in carotid atherosclerosis., Material/methods: Forty carotid atherosclerosis patients were enrolled. Patients were administrated olmesartan 20 mg/day for 3 months. Flow cytometry was used for counting circulating endothelial progenitor cells; colorimetric method was used to measure the serum levels of endothelial nitric oxide synthase and nitric oxide. Cell migration, adhesion, and proliferation capacity, and related signaling pathway were also analyzed. Spearman rank correlation analysis was used to investigate the influence of olmesartan on endothelial progenitor cells and clinical characteristics (e.g., sex, age, blood pressure)., Results: Compared with the control group, the number of circulating endothelial progenitor cells was significantly decreased. Olmesartan can increase circulating endothelial progenitor cells number and the serum levels of eNOS and NO. Furthermore, it can improve cell migration, adhesion, and proliferation capacities. Spearman rank correlation analysis showed there is no relationship between olmesartan promotion effects on endothelial progenitor cell mobilization and the clinical characteristics (P>0.05). P-eNOS and P-Akt expression can be unregulated by RNH-6270 treatment and blocked by LY294002., Conclusions: Olmesartan can effectively promote the endothelial progenitor cells mobilization and improve their function in patients with carotid atherosclerosis, independent of basic characteristics. This process relies on the PI3K/Akt/eNOS signaling pathway.