Comparative study on the predictive value of TG/HDL-C, TyG and TyG-BMI indices for 5-year mortality in critically ill patients with chronic heart failure: a retrospective study.

BACKGROUND: The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF). METHODS: Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan-Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve. RESULTS: Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29-1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000-1.003) and 1.01 (1.00-1.03), respectively. The K-M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571-0.645] vs. 0.558 [0.522-0.594] vs. 0.561 [0.524-0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant. CONCLUSION: As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF.

Association between insulin resistance and uncontrolled hypertension and arterial stiffness among US adults: a population-based study.

BACKGROUND: Prior research has established the correlation between insulin resistance (IR) and hypertension. While the association between triglyceride-glucose (TyG) index, a reliable surrogate marker of IR, and uncontrolled hypertension as well as arterial stiffness among individuals with hypertension remains undisclosed. METHODS: In this study, a total of 8513 adults diagnosed with hypertension from the National Health and Nutrition Examination Survey 1999-2018 were included. The primary outcome of the study are arterial stiffness (represented with estimated pulse wave velocity, ePWV) and uncontrolled hypertension. Logistic regression model, subgroup analysis, restricted cubic spine, and smooth curve fitting curve were conducted to evaluate the association between the IR indicators and uncontrolled hypertension and arterial stiffness in individuals with hypertension. RESULTS: Among included participants, the overall prevalence of uncontrolled hypertension was 54.3%. After adjusting for all potential covariates, compared with the first quartile of TyG index, the risk of uncontrolled hypertension increased about 28% and 49% for participants in the third quartile (OR, 1.28; 95% CI 1.06-1.52) and the fourth quartile (OR, 1.49; 95% CI 1.21-1.89) of TyG index, respectively. The higher OR of TyG index was observed in participants taking antihypertensive medication [fourth quartile versus first quartile (OR, 2.03; 95% CI 1.37-3.11)]. Meanwhile, we explored the potential association between TyG index and arterial stiffness and found that TyG index was significantly associated with increased arterial stiffness (ß for ePWV, 0.04; 95% CI 0.00-0.08; P = 0.039). However, traditional IR indicator HOMA-IR showed no significant positive correlation to uncontrolled hypertension as well as arterial stiffness in US adults with hypertension. CONCLUSION: Elevated levels of the TyG index were positive associated with prevalence of uncontrolled hypertension and arterial stiffness among US adults with hypertension.

Physical Exercise Modalities for the Management of Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

ABSTRACT: Different physical exercise modalities have been widely studied in patients having heart failure with preserved ejection fraction (HFpEF) but with variably reported findings. We, therefore, conducted a systematic review and meta-analysis to evaluate whether the efficacy of physical activity in the management of HFpEF is related to exercise modalities. PubMed and Embase were searched up to July 2021. The eligible studies included randomized controlled trials that identified effects of physical exercise on patients with HFpEF. Sixteen studies were included to evaluate the efficiency of physical exercise in HFpEF. A pooled analysis showed that exercise training significantly improved peak oxygen uptake (VO2), ventilatory anaerobic threshold, distance covered in the 6-minute walking test, the ratio of early diastolic mitral inflow to annular velocities, the Short Form 36 physical component score, and the Minnesota Living with Heart Failure Questionnaire total score. However, the changes in other echocardiographic parameters including the ratio of peak early to late diastolic mitral inflow velocities, early diastolic mitral annular velocity, and left atrial volume index were not significant. Both high-intensity and moderate-intensity training significantly improved exercise capacity (as defined by peak VO2), with moderate-intensity exercise having a superior effect. Furthermore, exercise-induced improvement in peak VO2 was partially correlated with exercise duration. Physical exercise could substantially improve exercise capacity, quality of life, and some indicators of cardiac diastolic function in patients with HFpEF. A protocol of moderate-intensity exercise training lasting a longer duration might be more beneficial compared with high-intensity training for patients with HFpEF.

Safety and effectiveness of a novel dielectric mapping system: one-year, two chinese centers experiences.

BACKGROUND: The KODEX-EPD system is a novel, dielectric three-dimensional mapping system. We aim to illustrate the feasibility, safety, and outcomes of ablation using the KODEX-EPD system. METHODS: A total of 272 patients with supraventricular arrhythmias were enrolled and underwent catheter ablation using the KODEX-EPD system from October 2020 to July 2021. The feasibility, safety, and ablation outcomes were analyzed. RESULTS: Of the enrolled patients, 15 (5.4%) had atrial tachycardia (AT), 88 (31.4%) had atrioventricular reentrant tachycardia (AVRT), 141 (50.4%) had atrioventricular nodal reentrant tachycardia (AVNRT), 34 (12.1%) had atrial fibrillation (AF), and 9 (3.2%) had atrial flutter (AFL). All AF patients included were first-do-pulmonary vein isolation (PVI); there were 26 paroxysmal AF and 8 persistent AF. All patients achieved immediate success of ablation. The mean follow-up duration was 11.8 ± 2.4 months. One patient (1.1%) in the AVRT subgroup and two patients (1.4%) in the AVNRT subgroup experienced recurrence. When considering a three-month blanking time, the estimated freedom of AF at one-year post-ablation with and without AADs was 75.7% and 70.4%, respectively. The Kaplan-Meier analysis showed no significant difference in the overall AF recurrence (log-rank; P = 0.931) or AAD-free AF recurrence (log-rank; P = 0.841) between RFCA and cryoablation. One patient had mild pulmonary embolism. None of the patients died or had a cerebrovascular event in the periprocedural period. CONCLUSIONS: This retrospective, two-center study demonstrated that catheter ablation of supraventricular arrhythmias using the KODEX-EPD system is feasible, safe, and effective. Trial registration Retrospectively registered.

Admission white blood cell count predicts post-discharge mortality in patients with acute aortic dissection: data from the MIMIC-III database.

BACKGROUND: Inflammation underlies both the pathogenesis and prognosis in patients with acute aortic dissection (AAD). This study aimed to assess the association of ICU admission of white blood cell count (WBCc) with post-discharge mortality in these patients. METHODS: Clinical data were extracted from the MIMIC-III V1.4 database. After adjusted to covariables, Cox regression analysis and Kaplan-Meier survival curve were performed to determine the relationship between WBCc on admission and post-discharge mortality (30-day, 90-day, 1-year and 5-year) in AAD patients. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were used to test the performance of WBCc in predicting mortality in AAD patients. RESULTS: A total of 325 eligible patients were divided into 2 groups: normal-WBCc group (≤ 11 k/uL) and high-WBCc group (> 11 K/uL). In univariate Cox regression analysis, high WBCc was significant risk predictor of 30-day, 90-day, 1-year and 5-year mortality [hazard ratio (HR), 95% CI, P 2.58 1.36-4.91 0.004; 3.16 1.76-5.70 0.000; 2.74 1.57-4.79 0.000; 2.10 1.23-3.54 0.006]. After adjusting for age and other risks, high WBCc remained a significant predictor of 30-day, 90-day and 1-year mortality in AAD patients (HR, 95% CI, P 1.994 1.058-3.76 0.033; 2.118 1.175-3.819 0.013; 2.37 1.343-4.181 0.003). The area under ROC curve of WBCc for predicting 30-day, 90-day, 1-year and 5-year mortality were 0.69, 0.70, 0.66 and 0.61, respectively. The results from subgroups analysis showed that there was no interaction in most strata and patients who were younger than 69 years of age or had history of respiratory disease with an elevated WBCc had an excess risk of 30-day mortality (HR, 95% CI, P 3.18 1.41-7.14 0.005; 3.84 1.05-14.13 0.043). CONCLUSIONS: Higher than normal WBCc on admission may predict post-discharge mortality in patients with AAD.

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

The omitted symptoms challenge the diagnosis of right atrial myxoma: a case report.

BACKGROUND: Cardiac myxoma (CM) is the most common type of primary cardiac tumors. The prevalence of primary cardiac tumors is 0.0017-0.28% in various autopsy studies. The clinical symptoms of CM which includes embolism, intracardiac obstruction, general or constitutional manifestations and infected myxoma are largely depended on the size, growing speed, location and pedicle length of the tumor. The following case reported a missed diagnostic case of a right atrial myxoma firstly presented digestive, systemic symptoms and immunologic disorder, leading to emergent tricuspid valves obstruction situation. CASE PRESENTATION: We reported a critical case of a 51-year-old female with CM was firstly admitted to the gastroenterology clinical department because of poor appetite, marked fatigability and weight loss for 2 months. The physician diagnosed her as chronic gastritis and treated her with some symptomatic treatment such as ilaprazole and magnesium aluminum carbonate. After months without definitive diagnosis, this right atrial myxoma grew into right ventricle and obstructed the tricuspid valves, causing her dyspnea, sweating, dizziness, feeling of impending death when she was sleeping. Transthoracic echocardiogram revealed a 6.1 × 4.2 × 3.7 cm2 mass adjacent to tricuspid valves. The patient underwent surgical excision and pathology revealed a primary cardiac myxoma. CONCLUSION: This case reported a critical result of missed diagnosis of right atrial myxoma and showed its systematic symptoms and immunologic disorder, highlighting the importance of systematic examinations on patients. Furthermore, it appeals early diagnosis of CM and consideration of drug targets to suppress CM development.

Identification of Target Genes and Transcription Factors in Mice with LMNA-Related Dilated Cardiomyopathy by Integrated Bioinformatic Analyses.

BACKGROUND Dilated cardiomyopathy (DCM), which is characterized by enlarged ventricular dimensions and systolic dysfunction, is the most common type of cardiomyopathy. Mutations in the LMNA gene are reported in approximately 10% of familial DCM cases. However, the mechanism of LMNA mutations in human DCM remains unclear. MATERIAL AND METHODS We used the GSE36502 and GSE123916 datasets to obtain gene expression profiles from LMNA-related DCM mice and to identify differentially expressed genes (DEGs). Crucial function and pathway enrichment analyses of DEGs were performed. Protein-protein interaction (PPI) network analysis was carried out to identify the top 10 hub genes, which were validated using reverse transcription-polymerase chain reaction (RT-PCR) to find target genes. Weighted gene co-expression network analysis (WGCNA) was used to explore the module relevant to external traits of LMNA-related DCM mice. Transcription factors (TFs) for the selected genes were analyzed using NetworkAnalyst. RESULTS A total of 156 common DEGs (co-DEGs) were identified, including 80 up-regulated and 76 down-regulated genes. The enriched biological functions and pathways were oxidative stress, regulation of apoptosis, regulation of fibrosis, and MAPK pathways. Five target genes (Timp1, Hmox1, Spp1, Atf3, and Adipoq) were verified after RT-PCR. Most co-DEGs were discovered to be related to the development of external traits. Three TFs (ELF1, ETS1, and NRF1) showed close interactions with the hub genes. CONCLUSIONS Our study used integrated bioinformatic analyses and revealed some important genes in mice with LMNA-related DCM, which could provide novel insights into the mechanism underlying human LMNA-related DCM.

[Risk factors for atrial fibrillation recurrence after catheter ablation].

The advent of catheter ablation technology has changed the treatment strategy for atrial fibrillation, and the efficacy of catheter ablation is accurate with small surgical trauma. Catheter ablation treatment of atrial fibrillation is significantly better than pharmacologic therapy of anti-arrhythmia and rate control. However, the clinic data of catheter ablation of atrial fibrillation show that the recurrence rate is high. The risk factors for recurrence after catheter ablation include age, sex, body mass index, related primary disease, left atrial volume, pulmonary vein volume, gene, atrial fibrillation types, surgery and so on. Regulation of the above factors is crucial in improving the clinical efficacy and prognosis of catheter ablation of atrial fibrillation.

[Research progress in NADPH oxidase family in cardiovascular diseases].

Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a major source of reactive oxygen species (ROS) in the cardiovascular system. The family of NOX includes seven isoforms, and expressed in different cardiovascular cell types and cell compartments, modulating multiple functions, such as cell proliferation, migration, differentiation, apoptosis, senescence, and inflammatory responses. The NOX-derived ROS are involved in many processes associated with cardiovascular diseases, such as hypertension, atherosclerosis, diabetic vascular disease, ventricular remodeling after myocardial infarction, and so on.

The role of losartan in preventing vascular remodeling in spontaneously hypertensive rats by inhibition of the H2O2/VPO1/HOCl/MMPs pathway.

Vascular peroxidase 1 (VPO1) has been proved to be associated with vascular endothelial cell apoptosis by producing reactive oxygen species. However, the contribution of VPO1 to the development of vascular remodeling (VR) remains to be fully characterized. We explored the role of VPO1 in VR in spontaneously hypertensive rats (SHRs) and the underlying mechanism of losartan in inhibiting VR. Compared to Wistar-Kyoto (WKY) rats, the SHR showed remodeling of their vascular walls. The level of VPO1 and the hydrogen peroxide (H2O2) concentration were increased in the SHRs. However, the SHRs pretreated with losartan showed significant inhibition of blood pressure and VR and decreased levels of VPO1 and H2O2 compared to the non-treated SHRs. Angiotensin II significantly increased the expressions of MMP-2, MMP-9 and the concentrations of H2O2 and hypochlorous acid (HOCl) in vascular smooth muscle cells (VSMCs). However, only the H2O2 level increased in VSMCs when transfected with VPO1 shRNA. These results support a critical but previously unrecognized role of VPO1 in VR and suggest that therapies to reduce VPO1 may be novel approaches for VR.

Protective Effects of α-Boswellic Acids in a Pulmonary Arterial Hypertensive Rat Model.

The purpose of this study was to observe the protective effects of α-boswellic acids on hypoxia-induced pulmonary vascular structural remodeling in pulmonary arterial smooth muscle cells in a hypertensive rat model. Pulmonary arterial smooth muscle cells were cultured and then randomly divided into four groups: normoxia, hypoxia (3 % O2; 24 h), hypoxia plus α-boswellic acids, and hypoxia plus DMSO (as a positive control), according to the different concentrations of α-boswellic acids (21.90 µM, 43.79 µM, and 87.58 µM). Apoptosis and proliferation of pulmonary arterial smooth muscle cells significantly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia and hypoxia plus DMSO groups (n = 8, p < 0.05). The mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 were significantly elevated in hypoxic cells compared with normal cells. However, the mRNA and protein phosphorylation levels of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 markedly decreased in the hypoxia plus α-boswellic acids group compared with the hypoxia plus DMSO group (n = 8, p < 0.05; n = 13, p < 0.05, respectively). Our findings suggest that α-boswellic acids can inhibit inappropriate apoptosis and excessive proliferation of pulmonary arterial smooth muscle cells and pulmonary vascular remodeling by repressing the expression of c-Jun N-terminal kinase 1 and extracellular regulated protein kinase 1 under hypoxic conditions.

[Research progress in the regulation of endothelial nitric oxide synthase activity and cardiovascular diseases].

Endothelial nitric oxide synthase (eNOS) is a major enzyme responsible for nitric oxide (NO) production. Both eNOS and NO play an important role in regulating vessel structure and function through participating in the physiological and pathological process. Generally, the phosphorylation of eNOS has been recognized as a common mechanism for regulation of eNOS function. However, recent studies have demonstrated several other new mechanisms, such as acetylation, S-glutathionylation, and protein-protein interaction. This review highlights the basic structure and functions of eNOS as well as the relationship between regulation of eNOS activity and cardiovascular diseases.

Regulation of endothelial progenitor cell differentiation and function by dimethylarginine dimethylaminohydrolase 2 in an asymmetric dimethylarginine-independent manner.

Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase-domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.

Involvement of anandamide transporter in calcitonin gene-related peptide expression stimulated by nitroglycerin and influence of ALDH2 Glu504Lys polymorphism.

The aim of this study was to investigate whether N-arachidonic acid ethanolamine (anandamide, AEA) transporter contributed to calcitonin gene-related peptide (CGRP) expression mediated by nitroglycerin (GTN) in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and its association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. In 10 ALDH2*2-genotyped Chinese volunteers, we assessed the activity of AEA transporter and expression of CGRP messenger ribonucleic acid (mRNA) in cultured PBMCs treated with different concentration of GTN with or without pretreatment with AM404 (the AEA transporter blocker). In this study, the activity of AEA transporter and expression of CGRP mRNA elevated with the increase in the concentration of GTN. Pretreatment of the cells with AM404 (1 µM) 2 hours before GTN reduced the GTN-induced increase in both AEA transporter activity and CGRP mRNA expression significantly, and cells with the ALDH2*1/*1 homozygote genotype showed significantly higher activity of AEA transporter and CGRP mRNA expression than carriers of the ALDH2*2 allele. Therefore, we strongly suggested that GTN can stimulate CGRP expression by elevating the AEA transporter activity, which is affected by ALDH2 Glu504Lys polymorphism.

Inhibitory effect of reinioside C on vascular smooth muscle cells proliferation induced by angiotensin II via inhibiting NADPH oxidase-ROS-ENK1/2-NF-kappaB-AP-1 pathway.

The proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin II (Ang II) plays a vital role in the pathogenesis of arteriosclerosis and restenosis. In the present study, the effect of reinioside C, a main active ingredient of Polygala fallax Hemsl, on proliferation of VSMCs induced by Ang II was investigated. It was found that Ang II (1 microM) markedly stimulated proliferation of VSMCs. Pretreatment of reinioside C (3, 10 or 30 microM) concentration-dependently inhibited the proliferative effect of Ang II. To determine the possible mechanism, NADPH oxidase subunits (Nox-1, Nox-4) mRNA expression, intracellular ROS level, phosphorylation of ERK1/2, NF-kappaB activity, and mRNA expression of AP-1 subunits (c-fos, c-jun) and c-myc were measured. The results demonstrated that reinioside C attenuated Ang II-induced NADPH oxidase mRNA expression, generation of ROS, ERK1/2 phosphorylation, activation of NF-kappaB, and mRNA expression of AP-1 and c-myc in VSMCs in a concentration-dependent manner. The effects of Ang II were also inhibited by diphenyleneiodonium (DPI, the NADPH oxidase inhibitor), PD98059 (the ERK1/2 inhibitor) and pyrrolidine dithiocarbamate (PDTC, the NF-kappaB inhibitor). These results suggest reinioside C attenuates Ang II-induced proliferation of VSMCs by inhibiting NADPH oxidase-ROS-ERK1/2-NF-kappaB-AP-1 pathway.

Meta-analysis of myeloperoxidase gene polymorphism and coronary artery disease susceptibility.

OBJECTIVE: To assess the association between myeloperoxidase (MPO) gene polymorphism and coronary artery disease (CAD). METHODS: Several databases were used to retrieve relevant literature up to March 2013 by keywords. A Meta-analysis was performed by Stata12.0 software to estimate the pooled odds ratio (OR) and the 95% confidence interval (CI). Heterogeneity among studies was tested and sensitivity analysis was applied. Publication bias was examined using Begg's funnel plot and Egger's linear regression test. RESULTS: A total of 17 studies were included in this Meta-analysis. For MPO -463 G/A polymorphism, the pooled OR of A allele vs G allele was 0.58 [95% CI (0.47-0.72)] and the pooled OR of genotypes AA+AG vs GG was 0.58 [95% CI (0.46-0.72)]. In subgroup analysis of study population, AA and AG genotypes were significantly associated with CAD in Asians but not in Europeans. The MPO -463 G/A polymorphism in the stable angina pectoris subgroup was evaluated in 3 studies and the pooled OR of A allele vs G allele and genotypes AA+AG vs GG for proven CAD was 0.45 [95% CI (0.15-1.37)] and 0.57 [95% CI (0.19- 1.65)]. For MPO -129 A/G gene polymorphism, the pooled OR of genotype GG vs AA+AG was 0.91 [95% CI (0.74-1.10)]. CONCLUSION: A allele of MPO -463 G/A gene is associated with decreased risk of CAD except in the Europeans. There is no association between MPO -129 A/G gene polymorphisms and CAD risk.

Shared Genetic Features of Psoriasis and Myocardial Infarction: Insights From a Weighted Gene Coexpression Network Analysis.

BACKGROUND: Increasing evidence suggests a higher propensity for acute myocardial infarction (MI) in patients with psoriasis. However, the shared mechanisms underlying this comorbidity in these patients remain unclear. This study aimed to explore the shared genetic features of psoriasis and MI and to identify potential biomarkers indicating their coexistence. METHODS AND RESULTS: Data sets obtained from the gene expression omnibus were examined using a weighted gene coexpression network analysis approach. Hub genes were identified using coexpression modules and validated in other data sets and through in vitro cellular experiments. Bioinformatics tools, including the Human microRNA Disease Database, StarBase, and miRNet databases, were used to construct a ceRNA network and predict potential regulatory mechanisms. By applying weighted gene coexpression network analysis, we identified 2 distinct modules that were significant for both MI and psoriasis. Inflammatory and immune pathways were highlighted by gene ontology enrichment analysis of the overlapping genes. Three pivotal genes-Src homology and collagen 1, disruptor of telomeric silencing 1-like, and feline leukemia virus subgroup C cellular receptor family member 2-were identified as potential biomarkers. We constructed a ceRNA network that suggested the upstream regulatory roles of these genes in the coexistence of psoriasis and MI. CONCLUSIONS: As potential therapeutic targets, Src homology and collagen 1, feline leukemia virus subgroup C cellular receptor family member 2, and disruptor of telomeric silencing 1-like provide novel insights into the shared genetic features between psoriasis and MI. This study paves the way for future studies focusing on the prevention of MI in patients with psoriasis.

Vascular VPO1 expression is related to the endothelial dysfunction in spontaneously hypertensive rats.

Reactive oxygen species (ROS) contributes to endothelial dysfunction that is involved in the pathogeneses of hypertension. Vascular peroxidase 1 (VPO1) can utilize ROS to catalyze peroxidative reactions, possibly enhancing endothelial dysfunction. This study is to identify VPO1's involvement in endothelial dysfunction and hypertension. Sixty-four spontaneously hypertensive rats (SHRs) and 64 age-matched, bodyweight controlled normotensive Wistar-Kyoto rats (WKYs) were randomly grouped and studied at the age of 5, 8, 13 and 20 weeks (16 animals, each). Blood pressure and vasodilator responses to acetylcholine in aortic rings were observed. The expressions of VPO1 and endothelial NO synthase (eNOS) in aortas were assessed by quantitative reverse transcription-PCR and western blotting analysis. Plasma concentrations of hydrogen peroxide (H2O2) and NO, NOX activity, hypochlorous acid (HOCl) production, and 3-nitrotyrosine content in aortic homogenates were also determined in this study. Along with the development of hypertension in SHR rats, VPO1 expression was up-regulated together with a significant increase in NOX activity, HOCl production, 3-nitrotyrosine content, and plasma H2O2 level compared with WKYs at 8, 13 and 20 weeks of age. In contrast, blood NO levels were decreased and aortic relaxation to acetylcholine was deteriorated in SHRs. The over-expression of VPO1 during the development of hypertension, accompanied by the endothelial dysfunction, the decreased NO levels, the elevated NOX and ROS activities, indicates a clear connection between VPO1 gene and hypertension. VPO1 may pathogenetically contribute to hypertension via signal pathways involving NOX-H2O2-VPO1-HOCl or JNK/p38 MAPK although further studies are needed to determine the precise mechanisms.

Targeted introduction of tissue plasminogen activator (TPA) at the AAVS1 locus in mesenchymal stem cells (MSCs) and its stable and effective expression.

Thrombolytic therapy using tissue plasminogen activator (TPA) is an effective method for treating acute myocardial infarction. However, the systemic administration of TPA is associated with the risk of hemorrhage. Mesenchymal stem cells (MSCs) from bone marrow are characterized by low immunogenicity and homing toward damaged tissues and are therefore ideal cell carriers to achieve lesion-targeting medication. In this article, TPA gene was integrated into the AAVS1 of mesenchymal stem cells, which has been confirmed to be a safe chromosomal locus. The targeting efficiency was 83%. The clones with the site-specific integration retained the stem cell traits of MSCs, displayed a normal karyotype and could persistently and effectively express TPA, as demonstrated by an average expression activity of 1.5 units/mL (3.4-fold that of the control group). After subculture and subsequent growth for two weeks, the clones showed an average TPA activity of 1.43 units/mL and exhibited no significant differences among the individual clones. In summary, the foreign TPA gene can be specifically introduced to the AAVS1 locus, whereby it can be stably and effectively expressed. MSCs can serve as cell carriers for the targeted treatment of a thrombus using TPA.