A5007330285- Antiplatelet Therapy and Cardiovascular Diseases
- Atherosclerosis and Cardiovascular Diseases
- Acute Myocardial Infarction Research
- Coronary Interventions and Diagnostics
- Cardiac Fibrosis and Remodeling
- Cardiac Imaging and Diagnostics
- Lipoproteins and Cardiovascular Health
- Adipokines, Inflammation, and Metabolic Diseases
- Signaling Pathways in Disease
- Cell Adhesion Molecules Research
- Inflammasome and immune disorders
- Cardiac Structural Anomalies and Repair
- Cardiovascular Disease and Adiposity
- Immune cells in cancer
- Cardiovascular Function and Risk Factors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Genetic Associations and Epidemiology
- Platelet Disorders and Treatments
- Immune Response and Inflammation
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Protease and Inhibitor Mechanisms
- RNA Interference and Gene Delivery
- Atrial Fibrillation Management and Outcomes
- MicroRNA in disease regulation
German Centre for Cardiovascular Research
2017-2025
Deutsches Herzzentrum München
2016-2025
Technical University of Munich
2016-2025
Deutsches Herzzentrum der Charité
2017-2022
München Klinik
2016-2021
Klinikum rechts der Isar
2021
Harvard University
2013-2018
Massachusetts General Hospital
2013-2018
Center for Systems Biology
2013-2018
Sage (United Kingdom)
2011-2018
Rationale : Macrophages populate the steady-state myocardium. Previously, all macrophages were thought to arise from monocytes; however, it emerged that, in several organs, tissue-resident may self-maintain through local proliferation. Objective Our aim was study contribution of monocytes cardiac-resident steady state, after macrophage depletion CD11b DTR/+ mice and myocardial infarction. Methods Results Using vivo fate mapping flow cytometry, we estimated that during state heart population...
Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging heart failure with preserved ejection fraction, remain unclear. Here we show that macrophages expand humans mice which was induced by either hypertension advanced age. A higher murine myocardial macrophage density results from monocyte recruitment increased hematopoiesis bone marrow spleen....
A group of healthy control subjects and patients with Parkinson's disease were investigated using positron emission tomography two tracers as indicators different specific properties the presynaptic dopaminergic system in caudate nucleus putamen. The first tracer, 6-L-(18F)-fluorodopa, was used an analog levodopa to assess its regional brain uptake, conversion into, retention dopamine further metabolites. second (11C)-nomifensine employed indicator striatal monaminergic reuptake sites that...
Macrophages reside in the healthy myocardium, participate ischemic heart disease, and modulate myocardial infarction (MI) healing. Their origin roles post-MI remodeling of nonischemic remote however, remain unclear.This study investigated number, origin, phenotype, function cardiac macrophages residing myocardium mice with chronic failure after coronary ligation.Eight weeks post MI, fate mapping flow cytometry revealed that a 2.9-fold increase results from both increased local macrophage...
Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood.
Rationale: The mechanisms leading to an expanded neutrophil and monocyte supply after stroke are incompletely understood. Objective: To test the hypothesis that transient middle cerebral artery occlusion (tMCAO) in mice leads activation of hematopoietic bone marrow stem cells. Methods Results: Serial vivo bioluminescence reporter gene imaging with tMCAO revealed cell cycling peaked 4 days ( P <0.05 versus pre tMCAO). Flow cytometry cycle analysis showed entire tree, including myeloid...
Nanoparticle-based delivery of simvastatin inhibits plaque macrophage proliferation in apolipoprotein E–deficient mice.
Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these cells, and response stem progenitor (HSPCs) to MI, however, is unclear. Here, we identify CCR2+CD150+CD48− LSK subset as most upstream contributor emergency myelopoiesis after ischemic organ injury. This has 4-fold higher proliferation rates than CCR2−CD150+CD48− displays differentiation bias,...
Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting secondary ischemic complications high mortality. We show that, ApoE(-/-) with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression adhesion molecules. To counteract the arterial recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key Simultaneously...
Heart failure following myocardial infarction (MI) remains one of the major causes death worldwide, and its treatment is a crucial challenge cardiovascular medicine. An attractive therapeutic strategy to stimulate endogenous mechanisms regeneration. This study evaluates potential with annexin A1 (AnxA1) induce cardiac repair after MI. AnxA1 knockout (AnxA1−/−) wild-type mice underwent MI induced by ligation left anterior descending coronary artery. Cardiac functionality was assessed...
The risk of early recurrent events after stroke remains high despite currently established secondary prevention strategies1. Risk is particularly in patients with atherosclerosis, more than 10% experiencing events1,2. However, the enormous medical burden this clinical phenomenon, underlying mechanisms leading to increased vascular and are largely unknown. Here, using a novel mouse model stroke-induced ischaemia, we show that leads activation AIM2 inflammasome vulnerable atherosclerotic...
Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular adhesion molecule 1 (VCAM-1)(+) macrophages are essential extramedullary because these use VCAM-1 retain HSCs spleen. Nanoparticle-enabled vivo RNAi silencing receptor for macrophage colony stimulation factor (M-CSFR) blocked...
Background: A chromosomal locus at 4q32.1 has been genome-wide significantly associated with coronary artery disease risk. The encompasses GUCY1A3 , which encodes the α 1 subunit of soluble guanylyl cyclase (sGC), a key enzyme in nitric oxide/cGMP signaling pathway. mechanism linking common variants this region risk is not known. Methods: Gene expression and protein were analyzed quantitative polymerase chain reaction immunoblotting, respectively. Putative allele-specific transcription...
Abstract Aims Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim investigate underlying mechanisms these contributions since they remain largely unclear. Methods results Here, we show in humans mice that leucocytes deplete rapidly from blood after a single episode acute mental stress. Using cell-tracking experiments animal models stress, found exposure leads prompt uptake inflammatory distinct tissues heart,...
Abstract Aims Targeting vascular inflammation represents a novel therapeutic approach to reduce complications of atherosclerosis. Neutralizing the pro-inflammatory cytokine interleukin-1β (IL-1β) using canakinumab, monoclonal antibody, reduces incidence cardiovascular events in patients after myocardial infarction (MI). The biological basis for these beneficial effects remains incompletely understood. We sought explore mechanisms IL-1β-targeted therapies. Methods and results In mice with...
Abstract The prevalence and public health burden of chronic heart failure (CHF) in Europe is steadily increasing mainly caused by the ageing population prolonged survival patients with CHF. Frequent hospitalizations, high morbidity mortality rates, enormous healthcare costs contribute to health-related burden. However, multidisciplinary frameworks that emphasize effective long-term management psychological needs are sparse. present position paper endorsed European Association Preventive...
Inflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients acute coronary syndrome chronic disease. However, biological basis these observations remains elusive. We sought explore mechanism by which colchicine...