IntroductionCardiovascular disease represents the leading cause of mortality among patients with chronic kidney disease (CKD). CKD-associated cardiomyopathy is characterized by pathological left ventricular hypertrophy and myocardial fibrosis. Pegmolesatide, a novel pegylated continuous erythropoietin receptor activator, has demonstrated efficacy in treating renal anemia. However, the biological effects of Pegmolesatide beyond erythropoiesis remain poorly characterized.MethodsThis study established a 5/6 nephrectomy rat model of CKD. The animals were randomized into four groups: sham-operated (Sham), sham-operated plus Pegmolesatide (Sham + Pegmolesatide), CKD model (CKD), and CKD model plus Pegmolesatide (CKD + Pegmolesatide). Cardiac function was assessed by echocardiography, while histopathological examination evaluated cardiac and renal structural changes. Serum renal function parameters were measured using biochemical assays. Myocardial expression of proteins and mRNAs related to fibrosis, hypertrophy, and associated signaling pathways was analyzed by Western blot and quantitative PCR. Furthermore, transcriptomic sequencing of myocardial tissue was performed, and in vitro experiments were conducted using AC16 human cardiomyocytes stimulated with serum from stage 5 CKD patients.ResultsTranscriptomic sequencing suggested that the cardioprotective effects of Pegmolesatide might be associated with improved mitochondrial function and modulation of the STAT3 signaling pathway. Results demonstrated that Pegmolesatide significantly improved cardiac functional parameters and attenuated both myocardial fibrosis and cardiomyocyte hypertrophy. Mechanistic investigations revealed that these cardioprotective effects were mediated through inhibition of JAK2/STAT3 signaling pathway activation and concomitant improvement of mitochondrial function.DiscussionThese findings demonstrate that pegmolesatide exerts anti-anemic effect-independent cardioprotection, offering novel insights into treating CKD-associated cardiomyopathy.

Marfan syndrome is a multisystem connective tissue disorder with age- and sex-related phenotypic variability. This study characterized early cardiovascular, valvular, transmitral filling, and skeletal phenotypes in Fbn1C1041G/+ mice. Male and female wild-type and Fbn1C1041G/+ mice were examined in independent age-specific cohorts from 4 to 20 weeks of age. Transthoracic echocardiography was used to measure aortic root and ascending aortic diameters, anterior mitral leaflet length, and mitral inflow Doppler parameters. Lateral X-ray imaging was used to quantify kyphosis angle. Fbn1C1041G/+ mice of both sexes showed age-related aortic enlargement, with segment-specific sex-related heterogeneity involving the annulus and sinus. In mutant mice, anterior mitral leaflet elongation was detected from 8 weeks in males and at 20 weeks in females. Reduced E-wave velocity and E/A ratio were observed in both sexes at 4 weeks, with E-wave velocity remaining lower at most subsequent ages and a lower E/A ratio present at all ages; A-wave velocity did not differ between genotypes at any examined age. Reduced kyphosis angle was detected from 4 weeks in females and from 12 weeks in males. These findings show that early Fbn1-related phenotypes follow organ-specific age-related patterns, supporting age-resolved and sex-stratified assessment in preclinical Marfan syndrome studies.

BACKGROUND:Cardiac lymphangiogenesis has been proposed as a potential therapeutic target to prevent the development of heart failure. However, the efficiency of systemically delivered VEGFC (vascular endothelial growth factor C) protein in inducing cardiac lymphangiogenesis has shown inconsistency across different studies. Moreover, the mechanisms underlying lymphatic remodeling during heart failure remain poorly understood. METHODS:To determine the role of lymphatic remodeling in heart failure, we used adeno-associated virus-mediated gene therapy to either inhibit VEGFR3 (vascular endothelial growth factor receptor 3) expression or enhance VEGFC expression in mice subjected to transverse aortic constriction. In vitro studies were further conducted to investigate the role of Yes-associated protein in VEGFC/VEGFR3 signaling in lymphatic endothelial cells. RESULTS:Our study shows that transverse aortic constriction induces dynamic lymphatic remodeling, characterized by an early adaptive cardiac lymphangiogenic response and enhanced peripheral lymphatic transport function. Adeno-associated virus-sh-VEGFR3 treatment inhibited this early adaptive lymphangiogenesis, exacerbating cardiac inflammation and adverse remodeling. Conversely, adeno-associated virus-VEGFC therapy appeared to be cardioprotective by promoting adaptive lymphangiogenesis and facilitating the resolution of cardiac inflammation. Moreover, adeno-associated virus-VEGFC treatment improved peripheral lymphatic drainage function, potentially alleviating peripheral congestion in heart failure. Further in vivo and in vitro analyses revealed that Yes-associated protein dephosphorylation is essential for VEGFC/VEGFR3 signaling-dependent lymphangiogenesis and for upregulation of lymphatic chemokines and scavenger receptors. CONCLUSIONS:These findings highlight that targeting cardiac lymphangiogenesis via VEGFC/VEGFR3 signaling through genetic approaches represents a promising therapeutic strategy for heart failure. Moreover, VEGFC administration may offer a novel, noninvasive decongestive approach by modulating the lymphatic system in heart failure management.

BACKGROUND:Heart failure (HF) guidelines recommend routine testing for iron deficiency (ID) and, for those with ID, intravenous iron if the left ventricular ejection fraction is <50%. Guideline adherence to these recommendations by cardiologists in China is unknown. METHODS AND RESULTS:An independent academic web-based survey was designed and distributed via social networks to cardiologists across China. Overall, 1342 cardiologists (median age 34 years, IQR 30-39, 51% women) from all provinces of China completed this survey. More than half were unaware of the need to screen for ID in HF and did not do so routinely in their clinical practice. Approximately 80% were not familiar with the diagnostic criteria for ID in HF guidelines, and only 0.8% recognised transferrin saturation <20% as an independent marker of ID. Regarding iron repletion, only 14% preferred intravenous to oral iron for correcting ID compared with 68% favouring oral iron. Three-quarters were unfamiliar with methods for calculating intravenous iron dose. Furthermore, over 80% were unaware that current guidelines only recommend ferric carboxymaltose or ferric derisomaltose for correcting ID. The main barriers to using intravenous iron were lack of knowledge and experience. Despite such poor awareness and practice, most cardiologists were interested in learning more about managing ID in HF. CONCLUSIONS:In this nationwide survey of cardiologists in China, we identified large gaps in both knowledge and management of ID. This survey will help guide the development of educational programmes to improve care for patients with HF and ID in China.

Myocardial work (MW) is a novel indicator measured by noninvasive echocardiography, which could detect subclinical myocardial dysfunction before reduction of left ventricular ejection fraction (LVEF). The study aimed to evaluate subclinical myocardial dysfunction in patients with systemic sclerosis (SSc) with normal LVEF, using left ventricular MW through two-dimensional speckle-tracking imaging (2D-STI). Eighty patients with SSc, which included 40 diffuse skin type SSc (dcSSc) and 40 limited skin type SSc (lcSSc) according to LeRoy’s criteria, and 40 gender and age matched health subjects were enrolled. The images were collected using standard transthoracic echocardiography. Global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained. Our study showed that there were no significant differences in LVEF and GLS between the SSc group and the control group. Both the lcSSc group and the dcSSc group had lower GWI, GCW, and GWE and higher GWW than the control group (P < 0.05). GWI, GCW, and GWE were lower in the dcSSc group than those in the lcSSc group, while GWW was higher in the dcSSc group (P < 0.05). GWI and GCW were positively correlated with LVEF (P < 0.001). GWI, GCW, and GWE were negatively correlated with GLS (P < 0.001), and GWW was positively correlated with GLS (P < 0.05). Elevated CRP was associated with reduced GWI and GCW (P < 0.05). Our study demonstrates the presence of subclinical myocardial dysfunction in SSc patients. The dcSSc patients may be more prone to have subclinical myocardial dysfunction than the lcSSc patients. Noninvasive left ventricular myocardial work may be a promising novel tool for detection of subclinical myocardial dysfunction.

Objective: To evaluate the diagnostic value of gene testing in familial hypercholesterolemia (FH) in patients with premature myocardial infarction(PMI). Methods: This study was a single center cross-sectional study. A retrospective analysis was made on PMI patients who visited the People's Hospital of Peking University from May 1, 2015 to March 31, 2017. Clinical data of patients was collected and gene testing of FH related genes low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B(APOB) and low density lipoprotein receptor adaptor protein 1(LDLRAP1) was carried out. Clinical diagnosis of FH patients was performed using Simon Broome criteria, DLCN criteria, and FH Chinese expert consensus. Results: There were 188 males (83.6%) among 225 PMI patients, and the age of the first myocardial infarction was (46.6±7.2) years old. Ten patients carried FH pathogenic or possibly pathogenic mutations (4.4%). Compared with Simon Broome standard, DLCN standard and FH Chinese expert consensus, gene testing increased the diagnostic rate of FH by 53.3%, 33.3% and 42.1% respectively. Conclusion: Gene testing is helpful to improve the diagnosis of FH, and it is important to start the standard treatment of FH as early as possible in patients with premature myocardial infarction.

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.

Background and ObjectivesEarly diagnosis of patients with acute myocardial infarction (AMI) who are at a high risk of heart failure (HF) progression remains controversial. This study aimed at identifying new predictive biomarkers of post-AMI HF and at revealing the pathogenesis of HF involving these marker genes.Methods and ResultsA transcriptomic dataset of whole blood cells from AMI patients with HF progression (post-AMI HF, n = 16) and without progression (post-AMI non-HF, n = 16) was analyzed using the weighted gene co-expression network analysis (WGCNA). The results indicated that one module consisting of 720 hub genes was significantly correlated with post-AMI HF. The hub genes were validated in another transcriptomic dataset of peripheral blood mononuclear cells (post-AMI HF, n = 9; post-AMI non-HF, n = 8). PRKAR1A, SDCBP, SPRED2, and VAMP3 were upregulated in the two datasets. Based on a single-cell RNA sequencing dataset of leukocytes from heart tissues of normal and infarcted mice, PRKAR1A was further verified to be upregulated in monocytes/macrophages on day 2, while SDCBP was highly expressed in neutrophils on day 2 and in monocytes/macrophages on day 3 after AMI. Cell–cell communication analysis via the “CellChat” package showed that, based on the interaction of ligand–receptor (L–R) pairs, there were increased autocrine/paracrine cross-talk networks of monocytes/macrophages and neutrophils in the acute stage of MI. Functional enrichment analysis of the abovementioned L–R genes together with PRKAR1A and SDCBP performed through the Metascape platform suggested that PRKAR1A and SDCBP were mainly involved in inflammation, apoptosis, and angiogenesis. The receiver operating characteristic (ROC) curve analysis demonstrated that PRKAR1A and SDCBP, as well as their combination, had a promising prognostic value in the identification of AMI patients who were at a high risk of HF progression.ConclusionThis study identified that PRKAR1A and SDCBP may serve as novel biomarkers for the early diagnosis of post-AMI HF and also revealed their potentially regulatory mechanism during HF progression.

Background Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anticancer therapy. Patients after completion of cancer-related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer-related comprehensive therapy. Methods. In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy, 45 non-breast cancer patients with metabolic syndrome, and 30 breast cancer patients without metabolic syndrome after therapy were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram. Results All the patients had normal LVEF. However, nine breast cancer patients with metabolic syndrome (20%) had GLS that was lower than –17%, while all the noncancer patients had normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with noncancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF and that use of trastuzumab for 1 year was a significant factor associated with reduction of GLS. In addition, breast cancer patients with metabolic syndrome had a decrease of GLS, compared with breast cancer patients without metabolic syndrome after cancer-related therapy. Conclusions Breast cancer patients with metabolic syndrome after completion of cancer-related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer-related comprehensive therapy.

To explore the potential targets underlying the effect of rosuvastatin on heart failure (HF) by utilizing a network pharmacology approach and experiments to identify the results. PharmMapper and other databases were mined for information relevant to the prediction of rosuvastatin targets and HF-related targets. Then, the rosuvastatin-HF target gene networks were created in Cytoscape software. Eventually, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, we constructed an HF animal model and used rosuvastatin to treat them, identifying the changes in heart function and related protein expression. We further used different cells to explore the mechanisms of rosuvastatin. Thirty-five intersection targets indicated the therapeutic targets linked to HF. GO analysis showed that 481 biological processes, 4 cellular components and 23 molecular functions were identified. KEGG analysis showed 13 significant treatment pathways. In animal experiments, rosuvastatin significantly improved the cardiac function of post-myocardial infarction mice and prevented the development of HF after myocardial infarction by inhibiting IL-1Β expression. Cell experiments showed that rosuvastatin could reduce the expression of IL-1B in HUVEC and THP-1 cells. The therapeutic mechanism of rosuvastatin against HF may be closely related to the inhibition of the expression of apoptosis-related proteins, inflammatory factors, and fibrosis-related genes. However, IL-1Β is one of the most important target genes.

目的 研究血管紧张素(Ang)家族新成员Ang-(1-9)对动脉粥样硬化中关键黏附分子血管细胞黏附分子1(VCAM-1)表达的作用及调控机制.方法 在体外培养人脐静脉内皮细胞,给予相应刺激进行分组:对照组;AngⅡ为实验1组;Ang-(1-9)为实验2组;Ang Ⅱ+Ang-(1-9)为实验3组;Ang Ⅱ+氯沙坦为实验4组;Ang Ⅱ+Ang-(1-9)+PD123319为实验5组.采用RT-PCR及流式细胞仪检测VCAM-1 mRNA及蛋白表达,荧光素酶报告基因检测法测定VCAM-1启动子活性,酶联免疫吸附法测定NF-κB细胞核内水平,细胞免疫荧光观察NF-κB细胞核内转移情况.结果 与对照组比较,实验1组VCAM-1 mRNA和蛋白表达明显增加(2.61±0.05 vs 1.00±0.00,146.35±1.81 vs 11.17±0.52,P＜0.05);与实验1组比较,实验3组和实验4组VCAM-1 mRNA和蛋白表达明显减少,差异有统计学意义(P＜0.05).与对照组比较,实验1组VCAM-1启动子活性和NF-κB在细胞核内表达明显增加,差异有统计学意义(P＜0.05);与实验1组比较,实验3组VCAM-1启动子活性和NF-κB在细胞核内表达明显降低,差异有统计学意义(P＜0.05);与实验3组比较,实验5组VCAM-1启动子活性和NF-κB在细胞核内表达明显增加,差异有统计学意义(P＜0.05).结论 Ang-(1-9)对VCAM-1的抑制作用有助于为动脉粥样硬化疾病的防治提供新思路.

BACKGROUND:Acute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF. METHODS:We performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above. RESULTS:In our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients. CONCLUSION:Our findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.

目的 系统性评价巨噬细胞移动抑制因子(MIF)基因启动子区-173多态性与冠状动脉粥样硬化性心脏病(CAD)发病风险之间的关系.方法 计算机检索中英文数据库,收集CAD与MIF基因启动子区-173多态性的病例对照研究.依据纳入标准和排除标准提取数据.Stata16.0软件进行系统分析.结果 共有10个研究被纳入meta分析.结果 显示,在4种遗传模型下,MIF基因启动子区-173位点单核苷酸多态性(SNP)与CAD发病风险具有相关性(等位基因模型OR=1.39;隐性基因模型OR=1.82;显性基因模型OR=1.43;纯合子基因模型OR=1.98),且该位点SNP中携带等位基因C是CAD的危险因素.亚组分析提示对于亚洲人群及非亚洲人群,该位点的SNP均与CAD发病风险相关.结论 本研究发现MIF基因启动子区-173多态性与CAD发病风险明显相关,且该位点SNP中携带等位基因C是CAD的危险因素.

Introduction: Genome-wide association studies revealed a robust association between genetic variants at the LIPA (lysosomal acid lipase) locus and coronary artery diseases (CAD). eQTL studies support that the risk alleles of LIPA CAD variants are associated with higher LIPA mRNA and enzyme activity in human monocytes, but not other blood or vascular cells, suggesting that increased myeloid LIPA may confer CAD risk. Herein, we aim to establish the causality of the variant-to-function relationship for the LIPA locus and elucidate how increased myeloid LIPA impact atherosclerosis in vivo. Hypothesis: We hypothesized that causal variants in LIPA lead to increased LIPA expression and enzyme activity in macrophages and myeloid-specific overexpression of Lipa promotes atherosclerosis. Results: We first confirmed that in human monocyte-derived macrophages, LIPA mRNA, protein and enzyme activity are higher in the risk allele carriers of CAD variants. High-resolution HiC revealed an intronic enhancer region showing strong interaction with the LIPA promoter. Within the enhancer region, both rs1320496 and rs1412445 had independent association with CAD and their risk alleles led to increased enhancer activity measured by luciferase assay. Risk allele of rs1320496 also demonstrated increased binding for PU.1, a myeloid-specific transcription factor. To establish how increased myeloid LIPA impact atherosclerosis, we generated myeloid-specific Lipa overexpression mice ( Lipa Tg , Ldlr -/- ). Lipa Tg significantly increased atherosclerotic lesion size without affecting plasma cholesterol level. scRNA-seq analysis showed that Lipa Tg led to reduced lipid-enriched yet increased inflammatory macrophage subsets, and upregulation of genes in chemokine signaling. This is further confirmed by reduced neutral lipid accumulation in both plaque and peritoneal macrophages in Lipa Tg mice. Mechanistically, Lipa Tg led to reduced expression of modified-LDL receptors, increased expression of inflammatory chemokines, and increased circulating IL18 and CXCL2 that likely drive immune cells infiltration during atherosclerosis. Conclusions: We for the first time established that LIPA risks alleles drive increased myeloid LIPA and aggravate atherosclerosis.

Herein, we designed several structures of GaAs/AIGaAs extended gate high electron mobility transistors (EG-HEMT) for cTnI detection, in order to explore the mechanism of bio-detection, the limit of detection (LOD) as well as the application in clinical detection. The experiment carried out that 50y structure of EG-HEMT biosensor, whose extended electrode is 50 times as large as the gate, has highest biological regulation ability (delta). Meanwhile, the concentration range of cTnI detection using 50y EG-HEMT biosensor is about 100 fg ml(-1) to 10 mu g ml(-1), which is much broader than that of Unicel Dx1800 (usually be used in clinical detection). Furthermore, due to the influence of parasitic resistance and other factors, delta increases with the increase of y, but the rising rate of delta decreases at the same time. By comparing the detecting results of clinical samples, 30y EG-HEMT is the best in the detection of cTnI concentration with a relative error of 6%. In a higher concentration range, it is more accurate than that of the Unicel Dx1800, breaking through its limit.

In this study, we developed extended-gate AlGaAs/GaAs HEMT sensors for accurate cTnI detection in serum. During the research, we found that blocking reagents whose molecule sizes are as large as the sizes of the target biomolecules can greatly improve the accuracy of detection. Based on this, the range of linear detection was significantly broadened, from 100 fg ml−1 to 1 ng ml−1. Additionally, 30y extended-gate HEMT sensors help to achieve accurate detection of cTnI in serum. The lowest relative errors of the 30y-structure were about 4%, which are greatly reduced as compared with the errors when using conventional sensors.

To perform a comprehensive meta-analysis of all available evidence on the efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction. We searched English and Chinese databases and calculated the weighted mean difference or standardized mean difference and 95% confidence intervals to estimate the efficacy and safety of renal denervation for heart failure. All relevant studies were screened and a meta-analysis was conducted using Review Manager 5.4. A total of 11 studies were identified for the meta-analysis. For the primary outcomes, the results showed that renal denervation significantly improved ejection fraction (weighted mean difference 6.42), left ventricular end-systolic diameter (weighted mean difference −3.95), left ventricular end-diastolic diameter (weighted mean difference −4.17) and left atrial diameter (weighted mean difference −4.09). For the secondary outcomes, renal denervation reduced the B-type natriuretic peptide level, heart rate, systolic blood pressure and diastolic blood pressure. However, further analysis revealed that renal denervation improved heart function but did not further reduce the heart rate and blood pressure compared with the control group. Treatment with renal denervation can significantly improve heart function and structure in patients with heart failure. In addition, the level of B-type natriuretic peptide can be reduced after renal denervation treatment. Renal denervation did not further reduce heart rate and blood pressure compared with the control group. Therefore, the treatment of heart failure with renal denervation is effective and safe.

Angiogenesis is an essential pathological feature of vulnerable atherosclerotic plaque. Exosome-derived microRNAs (miRNAs or miRs) have been proven to be important regulators of angiogenesis. However, the role of exosomes, which are secreted by endothelial cells (ECs) under conditions of oxidative stress, in angiogenesis remain unclear. The present study aimed to investigate the effects and mechanism of oxidative stress-activated endothelial-derived exosomes in angiogenesis. Exosomes were isolated from H2O2-stimulated human umbilical vein ECs (HUVECs; termed Exo(-H2O2)) by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis and western blot analysis. Exo(-H2O2) enhanced HUVEC proliferation, migration and tube formation, as determined by EdU incorporation assay, scratch wound migration assay and tube formation assay, respectively. miR-92a-3p was identified as the predominantly downregulated miRNA in the Exo(-H2O2)-treated HUVECs by small RNA sequencing, and the expression of primary miR-92a (pri-miR-92a-1) was also decreased, as shown by RT-qPCR. Similarly, the inhibition of miR-92a-3p promoted angiogenesis in vitro and in vivo. miR-92a-3p overexpression blocked the pro-angiogenic effects of Exo(-H2O2) on target ECs. Tissue factor (TF), a molecule involved in angiogenesis, was increased in HUVECs in which miR-92a-3p expression was downregulated, as shown by mRNA sequencing. TF was also predicted as a target of miR-92a-3p by using the RNA-hybrid program. The overexpression or suppression of miR-92a-3p modified TF expression at both the mRNA and protein level, as measured by RT-qPCR and western blot analysis, respectively. Luciferase reporter assays suggested that miR-92a-3p inhibited TF expression by binding to the 3' untranslated region of TF. On the whole, the findings of the present study demonstrate that exosomes released from oxidative stress-activated ECs stimulate angiogenesis by inhibiting miR-92a-3p expression in recipient ECs, and TF may be involved in the regulatory effects of miR-92a-3p on angiogenesis.