Evaluation of the Needs and Experiences of Patients with Hypertriglyceridemia: Social Media Listening Infosurveillance Study.

BACKGROUND: Hypertriglyceridemia is a risk factor for cardiovascular diseases. Internet usage in China is increasing, giving rise to large-scale data sources, especially to access, disseminate, and discuss medical information. Social media listening (SML) is a new approach to analyze and monitor online discussions related to various health-related topics in diverse diseases, which can generate insights into users' experiences and expectations. However, to date, no studies have evaluated the utility of SML to understand patients' cognizance and expectations pertaining to the management of hypertriglyceridemia. OBJECTIVE: The aim of this study was to utilize SML to explore the disease cognition level of patients with hypertriglyceridemia, choice of intervention measures, and the status quo of online consultations and question-and-answer (Q&A) search platforms. METHODS: An infosurveillance study was conducted wherein a disease-specific comprehensive search was performed between 2004 and 2020 in Q&A search and online consultation platforms. Predefined single and combined keywords related to hypertriglyceridemia were used in the search, including disease, symptoms, diagnosis, and treatment indicators; lifestyle interventions; and therapeutic agents. The search output was aggregated using an aggregator tool and evaluated. RESULTS: Disease-specific consultation data (n=69,845) and corresponding response data (n=111,763) were analyzed from 20 data sources (6 Q&A search platforms and 14 online consultation platforms). Doctors from inland areas had relatively high voice volumes and appear to exert a substantial influence on these platforms. Patients with hypertriglyceridemia engaging on the internet have an average level of cognition about the disease and its intervention measures. However, a strong demand for the concept of the disease and "how to treat it" was observed. More emphasis on the persistence of the disease and the safety of medications was observed. Young patients have a lower willingness for drug interventions, whereas patients with severe hypertriglyceridemia have a clearer intention to use drug intervention and few patients have a strong willingness for the use of traditional Chinese medicine. CONCLUSIONS: Findings from this disease-specific SML study revealed that patients with hypertriglyceridemia in China actively seek information from both online Q&A search and consultation platforms. However, the integrity of internet doctors' suggestions on lifestyle interventions and the accuracy of drug intervention recommendations still need to be improved. Further, a combined prospective qualitative study with SML is required for added rigor and confirmation of the relevance of the findings.

Gender disparities in the mediating role of symptom knowledge level in reducing acute coronary syndrome (ACS) decision delay: Findings from a community-based study in China.

BACKGROUND: Implementing training programs to educate patients on the prodromal symptoms of acute coronary syndrome (ACS) may assist patients in accurately recognizing these symptoms, and ultimately decrease their time delay in seeking emergency medical services (EMS). However, the effectiveness of this approach remains uncertain, particularly among the Chinese population. METHODS: A cross-sectional study was conducted within 22 communities in Beijing, China between 2015 and 2018, with a total of 1099 participants recruited. The study utilized a standardized questionnaire to evaluate the presence of intentional decision delay in turning to EMS under a hypothetical chest pain, the participants' knowledge of ACS prodromal symptoms, and whether they had ever received any training programs aimed at increasing their symptom knowledge. Mediation analysis was performed with regression models and bootstrapping methods, and gender difference was further analyzed through moderated mediation analysis. RESULTS: A total of 1099 participants (58.2% female, median [IQR] age 34 [20]) were included in the study. The results of the mediation analysis indicated that training programs were associated with a decrease risk in decision delay, with increased knowledge playing a mediating role (mediation effect/total effect = 36.59%, P < 0.0001). Gender modified this mediation effect, with it being observed only in the male group. Specifically, training programs were not found to significantly decrease decision delay among females (P > 0.05), even though they did improve women's knowledge of ACS prodromal symptoms (ß = 0.57, P = 0.012). CONCLUSION: The results suggested a relationship between prior training programs and reduced decision delay, with increased knowledge of prodromal symptoms of ACS serving as a mediator. However, the effect was only observed in male participants and not in female participants. This highlights the notion that mere transfer of knowledge regarding ACS prodromal symptoms may not be sufficient to mitigate decision delay in the female population. Further research is needed to corroborate these results and to gain deeper insights into the gender-specific barriers encountered in this study.

Isolated right ventricular Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND: Takotsubo cardiomyopathy can present itself in the most varied clinical forms, with extremely variable electrocardiogram anomalies and presence of comorbidities with a significant systemic commitment. Guillain-Barré Syndrome concomitant with isolated right ventricular Takotsubo cardiomyopathy is a rare entity. Here we present a patient with Guillain-Barré syndrome who had electrocardiogram abnormalities consistent with isolated right ventricular Takotsubo cardiomyopathy which have not been described in literature. This case report may prompt early identification of right ventricular involvement in neurological comorbidities, especially if the electrocardiogram is not frankly suggestive of an acute ischemic condition linked to coronary artery disease. CASE PRESENTATION: A 37-year-old woman was misdiagnosed as acute coronary syndrome because of abnormally elevated troponin T level and electrocardiogram findings in the Emergency Department. Due to absence of any significant stenosis in the main coronary artery, the primary diagnosis was ruled out. Based on reanalysis of the ECG abnormalities, the patient was diagnosed as a case of isolated right ventricular Takotsubo cardiomyopathy in Guillain-Barré Syndrome. This case demonstrates the importance of electrocardiogram as a critical tool to identify isolated right ventricular Takotsubo cardiomyopathy in Guillain-Barré Syndrome. Indeed, in this case, the electrocardiogram abnormalities were distributed beyond the territory of a single coronary artery distribution. CONCLUSIONS: The described electrocardiogram findings of isolated right ventricular Takotsubo cardiomyopathy in Guillain-Barré Syndrome may facilitate identification of right ventricular involvement in neurological diseases.

An Hypothesis: Disproportion Between Cardiac Troponin and B-Type Natriuretic Peptide Levels-A High Risk and Poor Prognostic Biomarker in Patients With Fulminant Myocarditis?

In our clinical practice, we recently found some patients with severe fulminant myocarditis (FM) who showed persistently elevated cardiac troponin (cTn) levels and "seemingly normal" B-type natriuretic peptide (BNP) level, and who subsequently progressed to poor outcomes. Indeed, this sounds contrary to conventional wisdom, but it is not an accidental phenomenon. Fulminant myocarditis is a rapidly progressive disease associated with high mortality. Recent studies have shown that patients with FM are significantly more likely to require heart transplantation than those without FM. Prompt diagnosis of FM and the institution of advanced cardiac life support will save more lives. Cardiac troponin and BNP are widely used diagnostic markers. Cardiac troponin is a specific marker of cardiac injury and its level correlates with the severity of cardiac injury. However, plasma BNP has a dual identity; it is not only a marker of cardiac pressure/volume overload, but it is also a cardioprotective factor that provides effective neurohormonal compensation to maintain homeostasis. Similar to fulminant hepatitis (characterised by diffuse inflammation and massive parenchymal cell necrosis) sometimes showing disproportion between transaminase level and bilirubin level, the disproportion between cTn and BNP levels in FM seems to be consistent with its severe histopathological changes, including diffuse infiltration of the myocardium by inflammatory cells, as well as severe cardiomyocyte injury and necrosis. Moreover, in previous studies, a lower BNP level was found to be an adverse prognostic marker in end-stage heart failure. All these findings indicate that in patients with FM with a persistently high cTn level and ominous clinical presentation, a "seemingly normal" BNP level is not a friendly signal. We hypothesise that the combination of a persistently elevated cTn level and low BNP level in patients with FM indicates worse myocardial injury and poor prognosis.

Efficacy and safety of catheter-based renal denervation for heart failure with reduced ejection fraction: a systematic review and meta-analysis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Lymphatic system identification, pathophysiology and therapy in the cardiovascular diseases.

The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the closed, high-pressure and circular blood vascular circulation, the lymphatic system forms an open, low-pressure and unidirectional transit network from the extracellular space to the venous system. It plays a key role in regulating tissue fluid homeostasis, absorption of gastrointestinal lipids, and immune surveillance throughout the body. Despite the critical physiological functions of the lymphatic system, a complete understanding of the lymphatic vessels lags far behind that of the blood vasculatures due to the challenge of their visualization. During the last 20 years, discoveries of underlying genes responsible for lymphatic vessel biology, combined with state-of-the-art lymphatic function imaging and quantification techniques, have established the importance of the lymphatic vasculature in the pathogenesis of cardiovascular diseases including lymphedema, obesity and metabolic diseases, dyslipidemia, hypertension, inflammation, atherosclerosis and myocardial infraction. In this review, we highlight the most recent advances in the field of lymphatic vessel biology, with an emphasis on the new identification techniques of lymphatic system, pathophysiological mechanisms of atherosclerosis and myocardial infarction, and new therapeutic perspectives of lymphangiogenesis.

Early diagnostic value of circulating microRNAs in patients with suspected acute myocardial infarction.

BACKGROUND/AIMS: Evidence has shown that several microRNAs (miRNAs) may be involved in coronary plaque rupture and local thrombus. However, the diagnostic ability of these miRNAs in acute myocardial infarction (AMI) is less known. The aim of this study is to explore the diagnostic value of these circulating miRNAs in patients presenting with acute chest pain in the emergency department. METHODS AND RESULTS: In a nested case-control study, 140 of 1,206 patients finally diagnosed with AMI were matched with 70 unstable angina and 70 noncardiac chest pain patients. Five candidate miRNAs (miR-483-5p, miR-155-5p, miR-451, miR-19b, and miR-223) were selected for validation. Among them, miR-19b, miR-223, and miR-483-5p were significantly higher in AMI patients compared with those without AMI. A multivariate analysis showed that these miRNAs were independent predictors of AMI. The overall areas under the receiver operating curves (AUCs) for miR-19b, miR-223, and miR-483-5p were 0.74, 0.65, and 0.70, respectively. However, serial sampling in AMI patients showed that these miRNAs already peaked on admission, which was earlier than troponin I. Among 170 patients with a negative troponin result at presentation, a panel of three miRNAs improved the discrimination ability to a clinical model. In 119 patients presenting within 3 hr after chest-pain onset, the diagnostic accuracy of each miRNAs was higher than Point of care (POC) troponin assay. And a panel of these miRNAs had an AUC of 0.92. CONCLUSION: Circulating miR-19b, miR-223, and miR-483-5p may provide clinically useful information for diagnosis in the early phases of AMI.

Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction.

BACKGROUND: The incidence of premature myocardial infarction (PMI) has gradually increased in recent years. Genetics plays a central role in the development of PMI. Familial hypercholesterolemia (FH) is one of the most common genetic disorders of cholesterol metabolism leading to PMI. OBJECTIVE: This study investigated the relationship between FH-associated genes and the phenotype of PMI to clarify the genetic spectrum of PMI diseases. METHOD: This study enrolled PMI patients (n = 225) and detected the mutations in their FH-associated genes (LDLR, APOB, PCSK9, LDLRAP1) by Sanger sequencing. At the same time, patients free of PMI (non-FH patients, n = 56) were enrolled as control, and a logistic regression analysis was used to identify risk factors associated with PMI. The diagnosis of FH was confirmed using "2018 Chinese expert consensus of FH screening and diagnosis" before the prevalence and clinical features of FH were analyzed. RESULTS: Pathogenic mutations in LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 17 of 225 subjects (7.6%), and all mutations were loss of function (LOF) and heterozygous. The genotype-phenotype relationship of patients carrying FH-associated mutations showed high heterogeneity. The logistic regression analysis showed that the smoking history, obesity and the family history of premature CHD were independent risk factors of PMI. In this study, a total of 19 patients (8.4%) were diagnosed as FH, and the proportion of smoking subjects in FH patients was higher than that in non-FH patients. CONCLUSIONS: FH-associated gene mutations were present in about 7.6% of Chinese patients with PMI. In addition to genetic factors, smoking history, lifestyle and other environmental factors may play a synergistic role in determining the phenotype of PMI. TRIAL REGISTRATION: Essential gene mutation of cholesterol metabolism in patients with premature myocardial infarction. ChiCTR-OCH-12002349.Registered 26 December 2014, http://www.chictr.org.cn/showproj.aspx?proj=7201 .

Endothelial microparticles-mediated transfer of microRNA-19b promotes atherosclerosis via activating perivascular adipose tissue inflammation in apoE-/- mice.

Microparticles(MPs) are the major carriers of circulating microRNAs. Our previous study has shown that microRNA (miR)-19b in endothelial cell-derived microparticles (EMPs) is significantly increased in patients with unstable angina. However, little is known about the relationship between miR-19b in EMPs and the progression of atherosclerosis. The aim of the present study was to define the role and potential mechanism of miR-19b incorporated in EMPs in the development of atherosclerosis. Western-diet-fed apoE-/- mice were injected with phosphate buffered solution(PBS), EMP carrying microRNA control(EMPcontrol) or miR-19b mimic (EMPmiR19b) intravenously. Systemic treatment with EMPmiR19b significantly accelerated carotid artery atherosclerosis progression by increasing lipid, macrophages and smooth muscle cells and decreasing collagen content in atherosclerotic plaque. Fluorescence-labelled EMPmiR19b injection proved that miR-19b could be transported into perivascular adipose tissue(PVAT) by EMPs. EMPmiR19b treatment also promoted inflammatory cytokines secretion and macrophages infiltration in PVAT. In further experiment, apoE-/- mice were divided into 3 groups: EMPcontrolPVAT(+), EMPmiR19bPVAT(+) and EMPmiR19bPVAT(-), based on removing or keeping pericarotid adipose tissue and injected with EMPcontrol or EMPmiR19b. Loss of PVAT attenuated EMPmiR19b-mediated effects on increasing carotid atherosclerosis formation and inflammatory cytokines level in plaque. EMPmiR19b inhibited suppressor of cytokine signaling 3 (SOCS3) expression in PVAT. Our findings demonstrate that miR-19b in EMPs exaggerates atherosclerosis progression by augmenting PVAT-specific inflammation proceeded by downregulating SOCS3 expression.

Plasmatic MicroRNA Signatures in Elderly People with Stable and Unstable Angina.

We aimed to investigate the distinctive miRNA profiles in the plasma of elderly patients with unstable angina (UA) and stable angina (SA), and to find more effective markers of UA in elderly people. We compared miRNA expression levels in plasma samples from 10 elderly patients with UA and 10 elderly patients with SA by using microarray-based miRNA chip, and then performed validation with Real-time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation (P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the highest discriminatory power in the diagnosis of elderly patients with UA (AUC: 0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs (mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI: 0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934) and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion, multi-miRNA panel could provide higher diagnostic value for the diagnosis of elderly patients with UA.

Modified high-throughput quantification of plasma microRNAs in heparinized patients with coronary artery disease using heparinase.

Heparin, a widely used anticoagulant in cardiovascular diseases, is notorious for its inhibitory effect on qRT-PCR-based detection. Heparinase I could degrade heparin in RNA. qRT-PCR-based TaqMan Low Density Array (TLDA) technology is commonly used for circulating microRNAs (miRNAs) profiling analysis. However, the effect of heparin contamination on inhibition of miRNAs TLDA amplification, as well as the method for removing heparin during this process, are not yet well investigated. We obtained the plasma RNA samples from patients undergoing percutaneous coronary intervention (PCI) before and after heparinization (n = 26). We found that heparin suppressed the miRNAs amplification by ∼8 cycles in the TLDA assay, which was absolutely reversed after treating the RNA samples with heparinase I using the components from TLDA reverse transcription system. We further observed that heparin inhibited the miRNAs amplification by ∼4 cycles in the qRT-PCR assay, which was also reversed by heparinase I using the similar method. Furthermore, we demonstrated that plasma miR-92a and miR-155 were differentially expressed in the patients undergoing PCI tested by TLDA assay, which was validated by qRT-PCR. In conclusion, we present a simple method for the removal of heparin with heparinase I, and for the subsequent successful miRNAs TLDA or RT-qPCR amplification.

Cited2 participates in cardiomyocyte apoptosis and maternal diabetes-induced congenital heart abnormality.

Gestational diabetes mellitus is a risk factor for abnormal heart development, but the molecular basis remains obscure. To further analyze this, the hyperglycemia rat and cell model were established in this study. The results showed that hyperglycemic rats gained significantly less weight during gestation than controls. The number of embryos per litter was significantly reduced in diabetic mothers compared to controls. Ventricular wall thickness was often decreased in the diabetic offspring and cardiomyocyte apoptosis participated in ventricular wall thinness. Our results also indicated that Cited2 expression decreased in the heart tissues of diabetic-exposed embryos comparing with the control. The vitro results showed that down-regulation of Cited2 was associated with high glucose-induced apoptosis in cardiomyocytes in vitro. Over-expression of Cited2 gene restrained the cardiomyocyte apoptosis induced by high glucose. Furthermore, Cited2 S192G mutation partly inhibited the capacity of Cited2 to suppress apoptosis induced by high glucose in cardiomyocytes. This showed the critical role of Cited2 in high glucose-induced cardiomyocytes apoptosis. Data from this study found the association of Cited2 down regulation with cardiomyocytes apoptosis and maternal diabetes-induced ventricular wall thinness genesis.

TRPV1 activation is involved in the cardioprotection of remote limb ischemic postconditioning in ischemia-reperfusion injury rats.

Limb remote ischemic postconditioning (RIPostC) has been proved to be a safe and effective measurement of cardioprotection against ischemia-reperfusion injury. But what bridges the remote organ insult and the cardioprotective effect in heart remains to be elucidated. This study aimed to found that whether TRPV1 may mediate the cardioprotective effect from remote organ to heart and the role of CGRP and SP in this process. We found that RIPostC effectively ameliorated cardiac ischemia/reperfusion injury in terms of limiting infarct size, lowering CK and cTnI release and improving cardiac function. In addition, these cardioprotective effects could be significantly abolished by inhibition of either CGRP or SP receptors with corresponding antagonists (CGRP8-37 for CGRP and RP-67580 for SP) injected before reperfusion. Besides, RIPostC resulted in significantly increase in the levels of CGRP and SP in plasma and hearts, as well as the levels and mRNA expression of CGRP and SP in DRG. The increase in CGRP and SP levels in plasma and hearts were markedly inhibited by TRPV1 receptor antagonist capsazepine. These findings indicate that limb remote ischemic postconditioning could attenuate cardiac ischemia/reperfusion injury in rats, and the cardioprotective mechanism is via TRPV1-mediated upregulation of CGRP and SP, which could subsequently act on their corresponding receptors in heart tissue.

MicroRNA-19b functions as potential anti-thrombotic protector in patients with unstable angina by targeting tissue factor.

The activation of a hemostatic system plays a critical role in the incidence of acute coronary events. Hemostatic proteins may be regulated by microRNAs (miRNAs). Microparticles (MPs) are the major carrier of circulating miRNAs. The aim of this study was to determine the potential role of miRNAs in regulating gene expression involved in the hemostatic system in patients with unstable angina (UA). MiRNA expression profiles in the plasma from patients with UA (UA group, n=9) compared with individuals with clinical suspicion of coronary artery disease (CAD) but negative angiography (control group, n=9) showed that among 36 differentially expressed miRNAs, miR-19b was the most obvious one. Using real-time PCR, 5 selected miRNA levels in plasma (UA group, n=20; control group, n=30) and plasma MPs (UA group n=6; control group n=6) were proved to be consistent with the miRNA array. Flow cytometry analysis indicated that the amounts of plasma endothelial microparticles (EMPs) were increased in UA patients (UA group, n=4) compared to controls (control group, n=4). In cultured endothelial cells (ECs), TNF-α increased miR-19b release and expression. Tissue factor (TF) was predicted to be the target of miR-19b by bioinformatics analysis. Luciferase reporter assays demonstrated that miR-19b binds to TF mRNA. Overexpression of miR-19b inhibited TF expression and procoagulant activity. This study indicates that in UA patients, the increase of miR-19b wrapped in EMPs due to endothelial dysfunction may partially contribute to the circulating miR-19b elevation and miR-19b may play an anti-thrombotic role by inhibiting the expression of TF in ECs.

Intervention effects of low-molecular-weight chondroitin sulfate from the nasal cartilage of yellow cattle on lipopolysaccharide-induced behavioral disorders: regulation of the microbiome-gut-brain axis.

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure-activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1ß, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.

Rosuvastatin Enhances Lymphangiogenesis after Myocardial Infarction by Regulating the miRNAs/Vascular Endothelial Growth Factor Receptor 3 (miRNAs/VEGFR3) Pathway.

BACKGROUND: Several clinical studies have suggested that the early administration of statins could reduce the risk of in-hospital mortality in acute myocardial infarction (AMI) patients. Recently, some studies have identified that stimulating lymphangiogenesis after AMI could improve cardiac function by reducing myocardial edema and inflammation. This study aimed to identify the effect of rosuvastatin on postinfarct lymphangiogenesis and to identify the underlying mechanism of this effect. METHOD: Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in mice orally administered rosuvastatin for 7 days. The changes in cardiac function, pathology, and lymphangiogenesis following MI were measured by echocardiography and immunostaining. EdU, Matrigel tube formation, and scratch wound assays were used to evaluate the effect of rosuvastatin on the proliferation, tube formation, and migration of the lymphatic endothelial cell line SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was measured by polymerase chain reaction (PCR) and Western blotting. A gain-of-function study was performed using miR-107-3p and miR-491-5p mimics. RESULTS: The rosuvastatin-treated mice had a significantly improved ejection fraction and increased lymphatic plexus density 7 days after MI. Rosuvastatin also reduced myocardial edema and inflammatory response after MI. We used a VEGFR3 inhibitor to partially reverse these effects. Rosuvastatin promoted the proliferation, migration, and tube formation of SVEC4-10 cells. PCR and Western blot analyses revealed that rosuvastatin intervention downregulated miR-107-3p and miR-491-5p and promoted VEGFR3 expression. The gain-of-function study showed that miR-107-3p and miR-491-5p could inhibit the proliferation, migration, and tube formation of SVEC4-10 cells. CONCLUSION: Rosuvastatin could improve heart function by promoting lymphangiogenesis after MI by regulating the miRNAs/VEGFR3 pathway.

Genome-wide analysis of methylation in rat fetal heart under hyperglycemia by methylation-dependent restriction site-associated DNA sequencing.

Diabetes mellitus causes an increased incidence of congenital heart malformations. However, the pathogenesis and potential epigenetic mechanism involved in this process are unclear. In this study, we used MethylRAD sequencing to compare changes in methylation levels in the genomic landscapes in the fetal heart in a rat model of hyperglycemia. Our results showed that methylation of CCGG/CCNGG sites were mostly enriched in intergenic regions, followed by intron, exon, upstream and the 5' and 3' untranslated regions. qRT-PCR results confirmed the MethylRAD sequencing findings, suggesting that abnormal CCGG/CCNGG methylation in the upstream region regulated gene expression. The differential methylation genes (DMGs) based on the CCGG and CCNGG sites in the upstream region were examined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene Ontology indicated that the CCGG-based DMGs involved in biological process and function were mainly related to transcription and co-SMAD binding. The CCNGG-based DMGs were mainly related to transcription and cytokine-mediated signaling pathways. Kyoto Encyclopedia of Genes and Genomes analysis indicated that CCGG-based DMGs were mainly involved in the Wnt signaling and TGF-ß signaling pathways. CCNGG-based DMGs were involved in the TNF signaling and apoptosis pathways. These genes may play dominant roles in cardiomyocyte apoptosis and heart disease and require further study. These genes may also serve as potential molecular targets or diagnostic biomarkers for heart malformations under hyperglycemia.

Case Report: Familial Pseudohyperkalemia Due to Red Blood Cell Membrane Leak in a Chinese Patient.

Hyperkalemia is a critical condition requiring careful evaluation and timely intervention. Many conditions could manifest as pseudohyperkalemia and it's important to differentiate them as inappropriate potassium-lowering therapy might lead to detrimental outcomes. A 56-year-old female was admitted for hyperkalemia (5.62-8.55 mmol/L). She had no symptoms or signs of hyperkalemia. A comprehensive work-up of hyperkalemia retrieved no valuable findings. Her blood samples underwent incubation tests at different temperatures and revealed temperature-dependent potassium leaks from red blood cells. Based on all test results, a diagnosis of hyperkalemia caused by red blood cell membrane defects was suspected. Whole-genome sequencing revealed a heterozygous c.1123C>T (p. R375W) mutation in the ABCB6 gene and confirmed the diagnosis of familial pseudohyperkalemia (FP). FP is an inherited benign condition in which red blood cells have increased cold-induced permeability to potassium. The patient was discharged with no additional treatment and she was suggested avoiding blood donation.

Endothelial Microparticle-Mediated Transfer of microRNA-19b Inhibits the Function and Distribution of Lymphatic Vessels in Atherosclerotic Mice.

In recent years, the function of the lymphatic system in atherosclerosis has attracted attention due to its role in immune cell trafficking, cholesterol removal from the periphery, and regulation of the inflammatory response. However, knowledge of the mechanisms regulating lymphangiogenesis and lymphatic function in the pathogenesis of atherosclerosis is limited. Endothelial microparticles carrying circulating microRNA (miRNA)s are known to mediate cell-cell communication, and our previous research showed that miRNA-19b in EMPs (EMPmiR-19b) was significantly increased in circulation and atherosclerotic vessels, and this increase in EMPmiR-19b promoted atherosclerosis. The present study investigated whether atherogenic EMPmiR-19b influences pathological changes of the lymphatic system in atherosclerosis. We first verified increased miR-19b levels and loss of lymphatic system function in atherosclerotic mice. Atherogenic western diet-fed ApoE-/- mice were injected with phosphate-buffered saline, EMPs carrying control miRNA (EMPcontrol), or EMPmiR-19b intravenously. The function and distribution of the lymphatic system was assessed via confocal microscopy, Evans blue staining, and pathological analysis. The results showed that lymphatic system dysfunction existed in the early stage of atherosclerosis, and the observed pathological changes persisted at the later stage, companied by an increased microRNA-19b level. In ApoE-/- mice systemically treated with EMPmiR-19b, the distribution, transport function, and permeability of the lymphatic system were significantly inhibited. In vitro experiments showed that miRNA-19b may damage the lymphatic system by inhibiting lymphatic endothelial cell migration and tube formation, and a possible mechanism is the inhibition of transforming growth factor beta receptor type II (TGF-ßRII) expression in lymphatic endothelial cells by miRNA-19b. Together, our findings demonstrate that atherogenic EMPmiR-19b may destroy lymphatic system function in atherosclerotic mice by downregulating TGF-ßRII expression.

Unusual course of congenital complete heart block in an adult: A case report.

BACKGROUND: Congenital complete heart block (CCHB) with normal cardiac structure and negativity for anti-Ro/La antibody is rare. Additionally, CCHB is much less frequently diagnosed in adults, and its natural history in adults is less well known. CASE SUMMARY: A 23-year-old woman was admitted to our hospital for frequent syncopal episodes. She had bradycardia at the age of 1 year but had never had impaired exercise capacity or a syncopal episode before admission. The possible diagnosis of acquired complete atrioventricular block was carefully ruled out, and then the diagnosis of CCHB was made. According to existing guidelines, permanent pacemaker implantation was recommended, but the patient declined. With regular follow-up for 28 years, the patient had an unusually good outcome without any invasive intervention or medicine. She had an uneventful pregnancy and led a normally active life without any symptoms of low cardiac output or syncopal recurrence. CONCLUSION: This case implies that CCHB in adulthood may have good clinical outcomes and does not always require permanent pacemaker implantation.