No abstract

Background Percutaneous transluminal coronary angioplasty (PTCA) represents an efficient therapeutic method for atherosclerosis but conveys a risk of causing restenosis. Endothelial colony-forming cell-derived exosomes (ECFC-exosomes) are important mediators during vascular repair. This study aimed to investigate the therapeutic effects of ECFC-exosomes in a rat model of atherosclerosis and to explore the molecular mechanisms underlying the ECFC-exosome-mediated effects on ox-LDL-induced endothelial injury. Methods The effect of ECFC-exosome-mediated autophagy on ox-LDL-induced human microvascular endothelial cell (HMEC) injury was examined by cell counting kit-8 assay, scratch wound assay, tube formation assay, western blot and the Ad-mCherry-GFP-LC3B system. RNA-sequencing assays, bioinformatic analysis and dual-luciferase reporter assays were performed to confirm the interaction between the miR-21-5p abundance of ECFC-exosomes and SIPA1L2 in HMECs. The role and underlying mechanism of ECFC-exosomes in endothelial repair were explored using a high-fat diet combined with balloon injury to establish an atherosclerotic rat model of vascular injury. Evans blue staining, haematoxylin and eosin staining and western blotting were used to evaluate vascular injury. Results ECFC-exosomes were incorporated into HMECs and promoted HMEC proliferation, migration and tube formation by repairing autophagic flux and enhancing autophagic activity. Subsequently, we demonstrated that miR-21-5p, which is abundant in ECFC-exosomes, binds to the 3’ untranslated region of SIPA1L2 to inhibit its expression, and knockout of miR-21-5p in ECFC-exosomes reversed ECFC-exosome-decreased SIPA1L2 expression in ox-LDL-induced HMEC injury. Knockdown of SIPA1L2 repaired autophagic flux and enhanced autophagic activity to promote cell proliferation in ox-LDL-treated HMECs. ECFC-exosome treatment attenuated vascular endothelial injury, regulated lipid balance and activated autophagy in an atherogenic rat model of vascular injury, whereas these effects were eliminated with ECFC-exosomes with knockdown of miR-21-5p. Conclusions Our study demonstrated that ECFC-exosomes protect against atherosclerosis- or PTCA-induced vascular injury by rescuing autophagic flux and inhibiting SIAP1L2 expression through delivery of miR-21-5p.

IntroductionThe aim of the study was to evaluate whether flow-mediated dilation (FMD) can be used to predict incident hypertension in patients with hyperuricemia.Material and methodsNormotensive participants with and without hyperuricemia at baseline were prospectively enrolled. Flow-mediated dilation was assessed at baseline, and after 1 year’s follow-up the incidence of hypertension was compared between those with and without hyperuricemia. The predictive value of baseline FMD for incident hypertension among hyperuricemia patients was evaluated.ResultsA total of 222 participants were included. Mean systolic and diastolic blood pressure (BP) was 129.5 ±8.4 mm Hg and 78.3 ±7.9 mm Hg. Mean serum uric acid (UA) level was 4.4 ±2.8 mg/dl. Mean FMD was 5.1 ±2.7%. Compared to normal UA group, hyperuricemia group had higher proportion of male (58.4% vs. 61.2%), higher systolic BP (125.4 ±7.9 mm Hg vs. 132.1 ±7.3 mm Hg), serum high sensitivity C-reactive protein (3.9 ±2.2 mg/dl vs. 4.5 ±3.0 mg/dl) and UA (3.5 ±1.4 mg/dl vs. 5.7 ±0.7 mg/dl) levels, but lower mean FMD (5.6 ±2.4% vs. 4.8 ±2.0%) (p < 0.05 for all comparisons). No participant in normal UA group developed hypertension, while in hyperuricemia group, 6 participants developed hypertension. In hyperuricemia participants, after adjusted for covariates, per 1-standard deviation decrease in baseline FMD remained significantly associated with 15% increased risk of incident hypertension.ConclusionsPatients with hyperuricemia have an increased risk of developing hypertension, and low baseline FMD in hyperuricemia patients is associated with significantly increased risk of incident hypertension.

Introduction The aim of the study was to evaluate the effects of cytochrome P450 2C19*2 ( CYP2C19 *2) on ischemic and bleeding events in the Chinese Han population. Material and methods Patients after coronary artery stenting were enrolled for genotyping CYP2C19 *2. Platelet reactivity 4 weeks after stent implantation was compared between different genotype groups. Ischemic and bleeding events were compared after 6 months’ follow-up. Results A total of 255 patients were enrolled and 57.7% and 42.3% of patients presented with stable angina and acute coronary syndrome, respectively. The prevalence of homozygous (AA) and heterozygous (GA) CYP2C19 *2 variants was 3.5% and 24.7% respectively, and the prevalence of wild type (GG) was 71.8%. Compared to GG and GA genotype groups, the absolute platelet activity reduction was significantly lower in AA genotype (GG 43.6 ±7.8%, GA 31.9 ±6.5%, and AA 24.8 ±5.3%, p < 0.01 for trend). After 6 months’ follow-up, 3.3%, 4.8% and 11.1% of patients experienced ischemic events in GG, GA and AA genotype groups, respectively ( p = 0.003 for trend). After adjusting for traditional risk factors, AA genotype was significantly associated with ischemic events, with hazard ratio 1.19 and 95% confidence interval 1.08–1.30 ( p = 0.013). Also, 2.2%, 1.6% and 0% of patients experienced bleeding events in GG, GA and AA genotype groups ( p = 0.153 for trend). No independent association of CYP2C19 *2 genotype and bleeding events was observed. Conclusions Genotyping of CYP2C19 *2 may be useful to guide antiplatelet treatment in the Chinese Han population. Randomized controlled trials are warranted to investigate whether genotype-guided antiplatelet treatment could reduce ischemic events.

The incidence of haemoglobinopathy is high in China, especially south of the Yangtze River. However, the exact status of haemoglobinopathy in Sichuan is unknown. To carry out a detailed research of haemoglobinopathy in individuals living in Sichuan, 13,298 subjects without clinical symptoms who were living in Sichuan Province, with an age distribution of 5–73 years, were included in this study. Between March 2014 and July 2017, these subjects received examinations at the Medical Lab of Chengdu Women's & Children's Central Hospital. Mean corpuscular volume (MCV) < 82 fL or mean corpuscular haemoglobin (MCH) < 27 pg was used to indicate haemoglobinopathy carriers. Abnormal haemoglobin was screened by electrophoresis, and genes were sequenced to identify genotypes. Genotype diagnosis of alpha- and beta-thalassaemia was carried out by using PCR and shunt hybridization. There were 638 suspected haemoglobinopathy carriers (4.80%, 638/13,298). DNA sequencing identified 6 subjects with abnormal haemoglobin genotypes and 15 subjects with Hb E. The frequency of heterozygosity for thalassaemia was 4.12% (1.48% for α-thalassaemia and 2.61% for β-thalassaemia) in Sichuan Province. The mutation spectrum of α-thalassaemia consisted of the five most common mutations: -- SEA , -α 3.7 , -α 4.2 , α CS , and α QS . Seven types of β-thalassaemia mutation were found in this study: CD41-42 (-TTCT) was the most frequent (28.47%), followed by 17 (A > T), −28 (A > G), and IVS-II-654 (C > T). The main abnormal haemoglobin genotype (HbE) and thalassaemia genotype (-- SEA , CD41-42 (-TTCT)) were consistent with those in other regions of China, but the carrier rate of β-thalassaemia in Sichuan was higher than that of α-thalassaemia.