A5001014545- Blood Coagulation and Thrombosis Mechanisms
- Atrial Fibrillation Management and Outcomes
- Antiplatelet Therapy and Cardiovascular Diseases
- Diet and metabolism studies
- Gut microbiota and health
- Cardiovascular Function and Risk Factors
- Diabetes Treatment and Management
- Heart Failure Treatment and Management
- Venous Thromboembolism Diagnosis and Management
- Biochemical Analysis and Sensing Techniques
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- IL-33, ST2, and ILC Pathways
- Metabolism and Genetic Disorders
- Fatty Acid Research and Health
- Clostridium difficile and Clostridium perfringens research
- Adipokines, Inflammation, and Metabolic Diseases
- Acute Myocardial Infarction Research
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
- Clinical Nutrition and Gastroenterology
- Metabolomics and Mass Spectrometry Studies
- Protease and Inhibitor Mechanisms
- Metabolism, Diabetes, and Cancer
Cleveland Clinic Lerner College of Medicine
2020-2025
Cleveland Clinic
2020-2025
Charité - Universitätsmedizin Berlin
2015-2024
Springer Nature (Germany)
2024
German Centre for Cardiovascular Research
2024
Deutsches Herzzentrum München
2024
Deutsches Herzzentrum der Charité
2024
Humboldt-Universität zu Berlin
2022-2024
Freie Universität Berlin
2022-2024
Heart and Diabetes Center North Rhine-Westphalia
2016
The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular pathogenesis animal models via modulation of adrenergic receptor signaling.
Abstract Aims Precision microbiome modulation as a novel treatment strategy is rapidly evolving and sought goal. The aim of this study to determine relationships among systemic gut microbial metabolite levels incident cardiovascular disease risks identify pathways possible targets for personalized therapeutic interventions. Methods results Stable isotope dilution mass spectrometry methods quantitatively measure aromatic amino acids their metabolites were used examine sequential subjects...
Abstract Background and Aims The pathways metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie alcohols also produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a substitute. Methods Untargeted metabolomics studies were performed on overnight fasting plasma samples discovery cohort (n = 1157) of...
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving remain unclear. Here we report that CD4+ T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), endogenous inhibitor tissue-protective cytokine IL-22. Using mouse models, demonstrate development requires cell-derived IL-22BP. Lastly, intestinal responsive...
Abstract Aims Gut microbiota and their generated metabolites impact the host vascular phenotype. The metaorganismal metabolite trimethylamine N-oxide (TMAO) is both associated with adverse clinical thromboembolic events, enhances platelet responsiveness in subjects. of TMAO on Tissue Factor (TF) vivo unknown. Here, we explore whether TMAO-enhanced thrombosis potential extends beyond effects platelets, linked to TF. We also further links between gut endothelial TF expression vivo. Methods...
Objective— Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity put those patients at risk thromboembolic events. Here, we sought investigate role micro-RNA (miR)–driven TF expression in diabetes mellitus. Approach Results— Plasma samples with were analyzed protein activity as well miR-126 before after optimization antidiabetic...
Heart failure with preserved ejection fraction (HFpEF) and pathological cardiac aging share a complex pathophysiology, including extracellular matrix remodelling (EMR). Protease-activated receptor 2 (PAR2) deficiency is associated EMR. The roles of PAR1 PAR2 have not been studied in HFpEF, age-dependent fibrosis, or diastolic dysfunction (DD).Evaluation endomyocardial biopsies from patients HFpEF (n = 14) revealed that reduced expression was aggravated DD increased myocardial fibrosis (r...
Abstract Background Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes (F) Xa generation resulting in a pro-thrombotic state cardiovascular complications. MicroRNA (miR)s impact gene on post-transcriptional level contribute homeostasis. Their distinct role control diabetes-related procoagulant remains poorly...
Phenylacetylglutamine (PAGln) is a phenylalanine-derived metabolite produced by gut microbiota with mechanistic links to heart failure (HF)-relevant phenotypes. We sought investigate the prognostic value of PAGln in patients stable HF.
Although artificial and non-nutritive sweeteners are widely used generally recognized as safe by the US European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly sweetener, clinically associated with heightened incident enhance thrombosis potential in vitro animal models. Effects dietary erythritol on...
Journal Article Xylitol and cardiovascular risks Get access Marco Witkowski, Witkowski Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USADepartment Medicine, Heart, Vascular Thoracic USA Present address: Cardiology, Angiology Intensive Care, German Heart Center Charité, Campus Benjamin Franklin, Berlin, Germany Friede Springer Prevention at for (DZHK), Partner Site Germany. Search other works by this...
Although antiplatelet therapy involving clopidogrel is a standard treatment for preventing cardiovascular events after coronary stent implantation, patients can display differential responses. Here, we assessed the effectiveness of on platelet function inhibition in subjects with and without type-2 diabetes stable artery disease. In addition, investigated correlation between routine clinical parameters.A total 64 heart disease were enrolled study. Among these, 32 had known diabetes, whereas...
According to the leaky gut concept, microbial products (e.g., lipopolysaccharide, LPS) enter circulation and mediate pro-inflammatory immunological responses. Higher plasma LPS levels have been reported in patients with various cardiovascular diseases, but not specifically during early atrial fibrillation (AF).We studied data blood samples from presenting first-diagnosed AF (FDAF) (n = 80) 20 controls.Circulating biomarkers that are suggestive of mucosal inflammation (zonulin, adhesion...
Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia inflammatory cytokines induce circulating tissue (TF) that promotes pro-thrombotic conditions in diabetes. It has recently become evident alterations of the post-transcriptional regulation TF via specific microRNA(miR)s, such as miR-126, contribute to pathogenesis diabetes its complications. The endothelial miR-19a involved homeostasis...
Background: Protease-activated receptor 1 (PAR1) and toll-like receptors (TLRs) are inflammatory mediators contributing to atherogenesis atherothrombosis. Vorapaxar, which selectively antagonizes PAR1-signaling, is an approved, add-on antiplatelet therapy for secondary prevention. The non-hemostatic, platelet-independent, pleiotropic effects of vorapaxar have not yet been studied. Methods Results: Cellular targets PAR1 signaling in the vasculature were identified three patient cohorts with...
Abstract Purpose Metformin is the first-line antidiabetic drug and shown to reduce cardiovascular risk independent from its glucose lowering action. Particularly in poorly controlled diabetes, tissue factor (TF) expressed vasculature accounts for thromboembolic complications. Here, we aimed assess effect of metformin on TF activity markers vascular inflammation type 2 diabetes. Methods In a cohort patients with uncontrolled diabetes (glycosylated hemoglobin 8.39 ± 0.24%, 68.1 2.6 mmol/mol, n...
Background: Atrial myopathy and atrial fibrillation (AF) accompany thrombo-inflammation. This facilitates disease progression promotes major adverse cardiovascular events (MACEs). Thrombin receptor (protease-activated 1, PAR1) signalling is central in mediating We hypothesised that PAR1 links coagulation inflammation through cytotoxic CD8+ T lymphocytes patients presenting with first-diagnosed AF (FDAF). Methods: A total of 210 were studied. included data blood samples from FDAF (n = 160),...
Abstract Background Risk stratification of patients with prediabetes is an unmet clinical need. Here, we examine the utility subclinical myocardial necrosis assessed by high-sensitivity cardiac troponin T (hs-cTnT) in predicting health outcomes stable subjects prediabetes. Methods hs-cTnT was analyzed a assay (Roche 5th generation) 2631 (HbA1c 5.7–6.4% or fasting glucose 100–125 mg/dL without previous diagnosis diabetes glucose-lowering therapy) who underwent elective coronary angiography...