A5070952146- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Protease and Inhibitor Mechanisms
- Sirtuins and Resveratrol in Medicine
- Cancer-related molecular mechanisms research
- Cerebrovascular and Carotid Artery Diseases
- Lipid metabolism and disorders
- Cardiovascular Health and Disease Prevention
- Mycobacterium research and diagnosis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antioxidant Activity and Oxidative Stress
- Nuclear Structure and Function
- S100 Proteins and Annexins
- Acute Ischemic Stroke Management
- Mitochondrial Function and Pathology
- Platelet Disorders and Treatments
- Inflammasome and immune disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Calcium signaling and nucleotide metabolism
- Circular RNAs in diseases
- Coronary Interventions and Diagnostics
- Diabetes Treatment and Management
- Nitric Oxide and Endothelin Effects
- Cardiac Fibrosis and Remodeling
- Biomarkers in Disease Mechanisms
University of Zurich
2019-2024
University Medical Center Utrecht
2019
Epidemiologic evidence links ischemic stroke to age, yet the mechanisms that underlie specific and independent effects of age on remain elusive, impeding development targeted treatments. This study tested hypothesis directly aggravates outcomes proposes inflamm-aging as a mediator potential therapeutic target.3 months- (young) 18-20 months-old (old) mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 minutes followed by 48 hours reperfusion. Old animals received weekly...
Abstract Aims Variants of the junctional cadherin 5 associated (JCAD) locus associate with acute coronary syndromes. JCAD promotes experimental atherosclerosis through large tumor suppressor kinase 2 (LATS2)/Hippo pathway. This study investigates role in arterial thrombosis. Methods and results knockout (Jcad−/−) mice underwent photochemically induced endothelial injury to trigger Primary human aortic cells (HAECs) treated small interfering RNA (siJCAD), LATS2 (siLATS2) or control siRNA...
Abstract The chronic inflammatory response plays an important role in adverse cardiac remodelling and the development of heart failure (HF). There is also evidence that pathogenesis several cardiovascular diseases, inflammation accompanied by antibody complement deposits heart, suggestive a true autoimmune response. However, antibody‐mediated immune responses HF progression less clear. We assessed whether cell infiltration immunoglobulin levels are associated with type disease stage, taking...
Arterial stiffness is a hallmark of vascular ageing that precedes and strongly predicts the development cardiovascular diseases. Age-dependent stiffening large elastic arteries primarily attributed to increased levels matrix metalloproteinase-2 (MMP-2). However, mechanistic link between age-dependent arterial MMP-2 remains unclear. Thus, we aimed investigate efficacy knockdown using small-interfering RNA (siRNA) on stiffness.Pulse wave velocity (PWV) was assessed in right carotid artery...
OBJECTIVE Long noncoding RNAs (lncRNAs) are involved in diabetogenesis experimental models, yet their role humans is unclear. We investigated whether circulating lncRNAs associate with incident type 2 diabetes older adults. RESEARCH DESIGN AND METHODS A preselected panel of was measured serum individuals without (n = 296) from the Vienna Transdanube Aging study, a prospective community-based cohort study. Participants were followed up over 7.5 years. second and 90) used to validate our...
Abstract Aims Arterial thrombosis as a result of plaque rupture or erosion is key event in acute cardiovascular events. Sirtuin 5 (SIRT5) belongs to the lifespan-regulating sirtuin superfamily and has been implicated ischaemic stroke cardiac hypertrophy. This project aims at investigating role SIRT5 arterial thrombus formation. Methods results Sirt5 transgenic (Sirt5Tg/0) knock-out (Sirt5−/−) mice underwent photochemically induced carotid endothelial injury trigger thrombosis. Primary human...
Background and aimsEarly revascularization -the gold standard therapy for ischemic stroke- is often withheld in the elderly population due to high risk of complications. Thus, safe effective preventive therapeutic options are needed. The plant-derived omega-3-fatty-acid alpha-linolenic-acid (ALA) has emerged as a novel cardiovascular-protective agent. As yet, little known about its potential effects on stroke. We hereby aimed investigate impact clinically relevant long-term dietary...
Abstract Aims Low-grade inflammation couples dysmetabolic states to insulin resistance and atherosclerotic cardiovascular (CV) disease (ASCVD). Selective sodium–glucose co-transporter 2 (SGLT-2) inhibition by empagliflozin improves clinical outcomes in patients with ASCVD independently of its glucose lowering effects. Yet, mechanism action remains largely undetermined. Here, we aimed test whether affects arterial thrombus formation baseline (BSL) conditions or low-grade inflammatory states,...
The role of junctional protein associated with coronary artery disease (JCAD) in acute ischemic stroke (AIS) has not been investigated yet. To investigate its potential as a therapeutic target, transient middle cerebral occlusion was induced JCAD knockout mice, improvement outcome and reduced blood-brain barrier permeability expression vascular cell adhesion molecule (VCAM)-1. plays deleterious ischemia/reperfusion damage associates higher 90-day mortality patients AIS. may thus represent...
Differential expression of long non-coding RNAs (lncRNAs) is a hallmark cardiovascular aging, cerebrovascular diseases, and neurodegenerative disorders. This research article investigates the association between panel lncRNAs risk death ischemic stroke in cohort non-institutionalized elderly subjects.
In a murine model of acute ischemic stroke, SIRT6 knockdown resulted in larger cerebral infarct size, worse neurological outcome, and higher mortality, indicating possible neuro-protective role SIRT6. this study, we aimed at evaluating the prognostic value serum levels patients with stroke (AIS). Serum SIRT6, collected within 72 h from symptom-onset, were measured 317 consecutively enrolled AIS COSMOS cohort. The primary endpoint analysis was 90-day mortality. independent assessed...
Microvesicles are vesicles shed by plasma membranes following cell activation and apoptosis. The role of lymphocyte-derived microvesicles in endothelial function remains poorly understood.CD4+ T cells isolated from peripheral blood healthy human donors were stimulated using anti-CD3/anti-CD28-coated beads. Proteomic profiling was performed linear discriminant analysis (LDA) activated (MV.Act) nonactivated (MV.NAct). In addition, data processing MaxQUANT workflow. Differentially expressed...
Abstract Background Patients with a recent acute coronary syndrome (ACS) remain at high residual cardiovascular risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute (1). The novel Junctional Protein Associated Coronary Artery Disease (JCAD) protein drives incident events via pathways, among them fibrinolysis, that act independently from lipid metabolism inflammation (2). Purpose Whether circulating JCAD provides predictive utility over above...
Abstract Background Takotsubo syndrome (TTS) is a stress-induced acute cardiomyopathy characterized by transient left ventricular (LV) dysfunction without obstructive coronary artery disease. TTS often underdiagnosed and undertreated typically occurs in middle-aged women who recover from initial symptoms within few weeks. Despite the apparent recovery, patients have worse cardiovascular prognosis compared to healthy individuals. To date, pathophysiology underlying remains unclear. So far,...
Abstract Introduction Aging is characterized by age-related vascular dysfunction, mainly caused endothelial dysfunction and arterial stiffness. Levels of nicotinamide adenine dinucleotide (NAD) decrease with aging accordingly, NAD thought to be involved in the progression dysfunction. Recent studies reported involvement CD38 regulation; indeed, its inhibition significantly prolongs lifespan progeroid aged mice. However, whether remains investigated. Methods expression was investigated aortic...
Abstract Background Aging is one of the most dominant cardiovascular (CV) risk factors. Sirt5 belongs to lifespan-regulating sirtuin superfamily as a protein deacylase. However, its regulatory effects on vascular function and aging are yet unclear. Purpose We therefore aimed investigate roles endothelial during aging, decipher underlying mechanisms, explore potential therapeutic target through in vivo vitro studies. Methods Aortic expression were studied C5BL/6 wild type (WT) mice followed...
Abstract Introduction Interleukin 6 (IL-6) has a pivotal role in atherothrombosis. Yet, targeting IL-6 to prevent atherothrombotic events still requires validation of efficacy and safety. The recent phase 2 RESCUE trial reported that direct inhibition ligand by the monoclonal antibody (mAb) Ziltivekimab is safe patients with elevated cardiovascular risk. Purpose This project investigated effects on arterial thrombosis, assessed underlying cellular mechanisms. Methods Three month old C56Bl/6...
Despite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved plasma cholesterol homeostasis recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition increasingly used different subsets of patients, including those...
Abstract Introduction Arterial thrombosis is an age-associated cause of myocardial infarction and stroke, which are the leading causes mortality morbidity worldwide. Hutchinson-Gilford Progeria Syndrome (HGPS) a rare genetic disorder that caused by point mutation in lamin A gene. It characterized progressive premature aging, decreased life expectancy. Two most frequent death children with HGPS ischemic stroke – cardiovascular events tightly linked to arterial thrombosis. Despite this fact,...