Subtle signs of atrial cardiomyopathy and left ventricular diastolic dysfunction are associated with reduced cognitive function: results from the Hamburg City Health Study.

Background: Atrial fibrillation is associated with cognitive dysfunction. Atrial cardiomyopathy has been correlated with both entities. We aimed to characterize the association of echocardiographic parameters of atrial cardiomyopathy with cognitive function and cerebral changes.

The phosphodiesterase 2A controls lymphatic junctional maturation via cGMP-dependent notch signaling.

The molecular mechanisms by which lymphatic vessels induce cell contact inhibition are not understood. Here, we identify the cGMP-dependent phosphodiesterase 2A (PDE2A) as a selective regulator of lymphatic but not of blood endothelial contact inhibition. Conditional deletion of Pde2a in mouse embryos reveals severe lymphatic dysplasia, whereas blood vessel architecture remains unaltered.

Antiplatelet drugs do not protect from platelet-leukocyte aggregation in coronary artery disease.

Background: Despite advances in cardiovascular medicine, coronary artery disease (CAD) remains a leading cause of mortality. Among the pathophysiological features of this condition, platelet-leukocyte aggregates (PLAs) require further attention, either as diagnostic/prognostic disease markers or as potential interventional targets.

Objectives: In this study, we characterized PLAs in patients with CAD.

Serial measurements of protein and microRNA biomarkers to specify myocardial infarction subtypes.

Background: While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies.

Methods: We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals.

The Tacrolimus Metabolism Rate and Dyslipidemia after Kidney Transplantation.

Fast tacrolimus (Tac) metabolism is associated with reduced survival rates after renal transplantation (RTx), mainly due to cardiovascular events. Because dyslipidemia is a leading cause of cardiovascular death, we hypothesized that most RTx patients do not achieve recommended target low-density lipoprotein cholesterol (LDL-C) levels (European cardiology society guidelines) and that fast Tac metabolizers have higher dyslipidemia rates. This study included RTx recipients who received initial immunosuppression with immediate-release tacrolimus (IR-Tac), mycophenolate, and prednisolone.

Biomarkers for Heart Failure Prognosis: Proteins, Genetic Scores and Non-coding RNAs.

Heart failure (HF) is a complex disease in which cardiomyocyte injury leads to a cascade of inflammatory and fibrosis pathway activation, thereby causing decrease in cardiac function. As a result, several biomolecules are released which can be identified easily in circulating body fluids. The complex biological processes involved in the development and worsening of HF require an early treatment strategy to stop deterioration of cardiac function.

Noncoding RNAs versus Protein Biomarkers in Cardiovascular Disease.

The development of more sensitive protein biomarker assays results in continuous improvements in detectability, extending the range of clinical applications to the detection of subclinical cardiovascular disease (CVD). However, these efforts have not yet led to improvements in risk assessment compared with existing risk scores. Noncoding RNAs (ncRNAs) have been assessed as biomarkers, and miRNAs have attracted most attention.

Aspirin, clopidogrel and prasugrel monotherapy in patients with type 2 diabetes mellitus: a double-blind randomised controlled trial of the effects on thrombotic markers and microRNA levels.

Background: Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM.

Materials And Methods: 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study.

Biomarkers in primary prevention : Meaningful diagnosis based on biomarker scores?

Cardiovascular (CV) risk assessment is based on the utilization of risk scores, enabling clinicians to estimate an individual's risk to develop CV pathologies and events. Such risk scores comprise classic CV risk factors such as smoking, diabetes, hypertension, and blood cholesterol levels. Recently, other CV biomarkers such as cardiac troponins have been suggested and evaluated as alternative biomarkers not only in the acute diagnostic setting of myocardial infarction, but also as markers for risk stratification in the general population.

Comparative Analysis of Circulating Noncoding RNAs Versus Protein Biomarkers in the Detection of Myocardial Injury.

Rationale: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are proposed novel biomarkers of myocardial injury. Their release kinetics have not been explored without confounding by heparin nor has their relationship to myocardial protein biomarkers.

Objective: To compare ncRNA types in heparinase-treated samples with established and emerging protein biomarkers for myocardial injury.

STAT1 regulates macrophage number and phenotype and prevents renal fibrosis after ischemia-reperfusion injury.

Renal ischemia-reperfusion injury (IRI) leads to acute kidney injury or delayed allograft function, which predisposes to fibrosis in the native kidney or kidney transplant. Here we investigated the role of the signal transducer and activator of transcription 1 (STAT1) in inflammatory responses following renal IRI. Our study showed that a subsequent stimulation of Janus-activated kinase 2/STAT1 and Toll-like receptor 4 pathways led to greater STAT1 activation followed by increased cytokine transcription compared with single-pathway stimulation in murine renal tubular cells.

microRNAs in cardiovascular disease - clinical application.

microRNAs (miRNAs) are well-known, powerful regulators of gene expression, and their potential to serve as circulating biomarkers is widely accepted. In cardiovascular disease (CVD), numerous studies have suggested miRNAs as strong circulating biomarkers with high diagnostic as well as prognostic power. In coronary artery disease (CAD) and heart failure (HF), miRNAs have been suggested as reliable biomarkers matching up to established protein-based such as cardiac troponins (cT) or natriuretic peptides.

Concomitant implantation of Impella on top of veno-arterial extracorporeal membrane oxygenation may improve survival of patients with cardiogenic shock.

Aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support stabilizes patients with cardiogenic shock. Despite improved oxygenation and peripheral circulation, LV unloading may be impeded due to the increased afterload, resulting in a failing static left ventricle and in high mortality.

Methods And Results: We describe for the first time a large series of patients treated with the combination of VA-ECMO and Impella compared with patients with VA-ECMO only.

Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study.

Introduction: Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease.

Diagnostic and prognostic value of circulating microRNAs in heart failure with preserved and reduced ejection fraction.

microRNAs (miRNAs) are powerful regulators of posttranscriptional gene expression and play an important role in pathophysiological processes. Circulating miRNAs can be quantified in body liquids and are promising biomarkers in numerous diseases. In cardiovascular disease miRNAs have been proven to be reliable diagnostic biomarkers for different disease entities.

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.

Background: Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD.

EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

Background: Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA.

microRNA-based diagnostics and therapy in cardiovascular disease-Summing up the facts.

Circulating microRNAs (miRNAs) are discussed as potential disease-specific biomarkers in cardiovascular disease. Their diagnostic value has been examined in numerous studies and animal models with respect to coronary artery disease (CAD) and myocardial infarction (MI) and the prognostic abilities of circulating miRNAs in risk stratification of future disease have been evaluated. Various miRNAs are described to complement protein-based biomarkers or classical risk factors in the diagnosis of CAD or MI and even represent potential new biomarkers in the discrimination of unstable angina pectoris (UAP).

Extracapsular lymph node spread: a new prognostic factor in gastric cancer.

Background: Lymphatic spread is 1 of the most relevant prognostic factors for gastric carcinoma. The current International Union Against Cancer (UICC) pN staging system is based on the number of metastatic lymph nodes and does not take into consideration the characteristics of the metastatic lymph nodes itself. The aim of the current study was to examine the prognostic value of extracapsular lymph node involvement in gastric cancer and to find correlations with clinicopathological parameters.

Early gastric cancer: lymph node metastasis starts with deep mucosal infiltration.

Objective: The purpose of this study was to evaluate the frequency of lymph node metastasis according to the depth of tumor infiltration of the mucosa and submucosa.

Background Data: Currently some endoscopists extend the indication for endoscopic mucosal resection in gastric cancer to the submucosa. However, the decision between endoscopic mucosectomy or gastrectomy with lymphadenectomy for early gastric cancer depends especially on the probability of lymph node metastasis.

Quantitative analysis of survivin RNA expression in blood as a non-invasive predictor of response to neoadjuvant radiochemotherapy in esophageal cancer.

Background And Objectives: Analysis of survivin RNA expression in peripheral blood as a non-invasive molecular predictor of response to neoadjuvant radiochemotherapy in patients with locally advanced cancer of the esophagus.

Material And Methods: Blood samples were drawn from 29 patients with esophageal cancer prior to neoadjuvant radiochemotherapy. After extraction of cellular tumor-RNA from blood samples, quantitative expression analysis of survivin was done by quantitative real-time RT-PCR.