A5050964893- Cardiac Fibrosis and Remodeling
- Atherosclerosis and Cardiovascular Diseases
- Signaling Pathways in Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Disease and Adiposity
- Inflammation biomarkers and pathways
- Cardiovascular Function and Risk Factors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Eicosanoids and Hypertension Pharmacology
- Psoriasis: Treatment and Pathogenesis
- Heart Failure Treatment and Management
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- S100 Proteins and Annexins
- Aortic aneurysm repair treatments
- Aortic Disease and Treatment Approaches
- Pancreatic function and diabetes
- Thermoregulation and physiological responses
- Genetics, Aging, and Longevity in Model Organisms
- Renin-Angiotensin System Studies
- Macrophage Migration Inhibitory Factor
- Adipokines, Inflammation, and Metabolic Diseases
- Endoplasmic Reticulum Stress and Disease
- Alcohol Consumption and Health Effects
- Adipose Tissue and Metabolism
University Medical Center of the Johannes Gutenberg University Mainz
2015-2024
Johannes Gutenberg University Mainz
2015-2024
German Centre for Cardiovascular Research
2019-2023
Abstract Aim Recent evidence suggests that arterial hypertension could be alternatively explained as a physiological adaptation response to water shortage, termed aestivation, which relies on complex multi‐organ metabolic adjustments prevent dehydration. Here, we tested the hypothesis chronic loss across diseased skin leads similar adaptive conservation responses observed in experimental renal failure or high salt diet. Methods We studied mice with keratinocyte‐specific overexpression of...
Traffic noise may play an important role in the development and deterioration of ischaemic heart disease. Thus, we sought to determine mechanisms cardiovascular dysfunction inflammation induced by aircraft a mouse model myocardial infarction (MI) humans with incident MI.C57BL/6J mice were exposed alone (average sound pressure level 72 dB; peak 85 dB) for up 4 days, resulting pro-inflammatory aortic gene expression myeloid cell adhesion/diapedesis pathways. The promoted adhesion infiltration...
Abstract Alcoholic cardiomyopathy (ACM) resulting from excess alcohol consumption is an important cause of heart failure (HF). Although it assumed that the cardiotoxicity ethanol (EtOH)-metabolite acetaldehyde (ACA) central for its development and progression, exact mechanisms remain obscure. Murine cardiomyocytes (CMs) exposed to ACA or EtOH showed increased superoxide (O 2 •−) levels decreased mitochondrial polarization, both being normalized by NADPH oxidase (NOX) inhibition. C57BL/6 mice...
Abstract Aims Heart failure (HF) ensuing myocardial infarction (MI) is characterized by the initiation of a systemic inflammatory response. We aimed to elucidate impact myelomonocytic cells and their activation angiotensin II on vascular endothelial function in mouse model HF after MI. Methods results was induced male C57BL/6J mice permanent ligation left anterior descending coronary artery. Compared sham, had significantly impaired accompanied enhanced mobilization Sca-1+c-Kit+...
Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify profibrotic coagulation signaling pathway that can be targeted improved function following with persistent ischemia. Quantitative phosphoproteomics tissue revealed an upregulated mitogen-activated protein kinase (MAPK) human IHF. Intervention this trametinib...
Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial are associated dysregulation of neurohormonal axis. How activation linked to shortening in pathogenesis incompletely understood. Cardiomyocyte length was assessed a mouse model hypertensive induced by excess (AngII [angiotensin II] infusion, high salt diet, uninephrectomy), AngII-stimulated cardiomyocytes endomyocardial biopsies from...
The neutrophil recruiting cytokine Interleukin-17A (IL-17A) is a key component in vascular dysfunction and arterial hypertension. Moreover, IL-17A has central role for the infiltration of myeloid cells into wall Angiotensin II-induced inflammation. intention our study was to analyze impact T cell-derived on hypertension, function, Chronic overexpression (CD4-IL-17Aind/+ mice) resulted elevated reactive oxygen species peripheral blood significant compared control mice. seen CD4-IL-17Aind/+...
Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, microglia, multiple organs harbor at least two subtypes other steady state. During certain circumstances, like tissue insult, additional recruited to from monocyte pool. Previously, a macrophage population marked by expression Spp1, Cd9, Gpnmb, Fabp5, Trem2, has been described in several models organ injury cancer,...
Myelomonocytic cells are critical in injury and healing post-myocardial infarction (MI). Mechanisms of regulation, however, incompletely understood. The aim the study was to elucidate role interferon gamma (IFN-γ) orchestrated inflammatory response a murine model MI.MI induced 8- 12-week-old male mice (C57BL/6 background) by permanent ligation left anterior descending (LAD) coronary artery. Lysozyme M (LysM)+ cell-depleted LysMiDTR transgenic displayed reduced influx...
The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well cardiovascular disease progression. Since myeloid cells are primary source of IL-6 formation, we aimed to generate mouse model study cell-derived vascular disease.
Pulmonary embolism (PE) results from deep vein thrombosis (DVT) and can lead to chronic thromboembolic pulmonary hypertension (CTEPH) involving vascular dysfunction. Mechanisms are incompletely understood, in part due lack of mouse models. We induced PE C57BL/6 mice by intravenous injection thrombin (166 U/kg BW), confirmed a sudden bradycardia, bradypnea, an increase artery (PA) pressure observed high-frequency ultrasound. While symptoms resolved rapidly after single application, repeated...
Excess fibrotic remodeling causes cardiac dysfunction in ischemic heart disease, driven by MAP (mitogen-activated protein) kinase-dependent TGF-ß1 (transforming growth factor-ß1) activation coagulation signaling of myeloid cells. How coagulation-inflammatory circuits can be specifically targeted to achieve beneficial macrophage reprogramming after myocardial infarction (MI) is not completely understood.
Aims: Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a cornerstone of drug therapy after myocardial infarction (MI) and improve left ventricular function survival. We aimed to elucidate the impact early treatment with ACE inhibitor ramipril on hematopoietic response MI, as well chronic systemic vascular inflammation. Methods Results: In mouse model induced by permanent ligation anterior descending artery, immediate initiation (10 mg/k/d via drinking water) reduced cardiac...
The prototypic protein disulfide isomerase (PDI), encoded by the P4HB gene, has been described as a survival factor in ischemic cardiomyopathy. However, role of associated 6 (PDIA6) under hypoxic conditions myocardium remains enigmatic, and it is unknown whether gut microbiota influences expression PDI PDIA6 acute myocardial infarction. Here, we revealed that, addition to PDI, family member PDIA6, regulator unfolded response, upregulated mouse cardiomyocyte cell line HL-1 when cultured...
Myeloid cells are crucial for the development of vascular inflammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial and platelets has been implicated in cardiovascular diseases. Our aim was to evaluate role LRP8, particular from immune cells, Methods. LRP8+/+ LRP8−/− mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day 7 28 day) using osmotic minipumps. Blood pressure...
Abstract Background Excess fibrotic remodeling leads to cardiac dysfunction in ischemic heart disease and is driven by MAP kinase-dependent transforming growth factor-ß1 (TGF-ß1) activation coagulation signaling of myeloid cells. How coagulation-inflammatory circuits can be specifically targeted achieve beneficial macrophage reprogramming after myocardial infarction (MI) incompletely understood. Methods Mice with permanent ligation the proximal left anterior descending artery (LAD) were used...
Background: Heart failure (HF) after myocardial infarction (MI) leads to impaired left ventricular function and reduced blood flow in peripheral arteries. Angiotensin II (ATII) signaling is crucial MI, inflammatory myelomonocytic cells are involved the process of ATII-induced vascular dysfunction. Their role MI-mediated dysfunction has not been defined yet. Objective: Test impact selective depletion lysozyme M positive (LysM+) on endothelial a model ischemic heart mice Methods results: 8 12...
Introduction: Interleukin-17A is important in the development of vascular dysfunction. However, mechanism behind still not completely understood. The aim our study was to investigate if IL-17A overexpression T cells induces dysfunction mainly via inflammatory cell recruitment vessel wall or there are other mechanisms behind. Methods: We used a mouse model specific (CD4-IL-17A ind/+ mice) and ubiquitous IL-17 receptor A knockout (IL-17RA del mice). Vascular induced Angiotensin-II (Ang-II,...
Abstract Background In the setting of myocardial infarction (MI), patients with coronary no-reflow and/or delayed presentation after onset symptoms (sub-acute MI) are inflicted by severe thrombo-inflammation and marked worse clinical outcome. However, it is unclear whether tissue factor (TF) contributes to outcome post MI solely regulatory functions its cytoplasmic tail independently coagulation activity. Purpose We analyzed role TF domain in recruitment myeloid cells into infarcted...
Abstract Background Ischemic heart failure (HF) ensuing myocardial infarction (MI) leads to impaired left ventricular function, reduced cardiac output and counterregulatory activation of angiotensin II (AngII) levels. Furthermore, it is characterized by the initiation a systemic inflammatory response. Objective We aimed elucidate impact myelomonocytic cells their on vascular endothelial function in mouse model HF after MI. Results was induced male C57BL/6J mice permanent ligation anterior...
Abstract Background/Objectives Myeloid cells are crucial for the development of vascular infammation. Low-density lipoprotein receptor-related protein 8 (LRP8) or Apolipoprotein E receptor 2 (ApoER2), is expressed by macrophages, endothelial and platelets has been implicated in cardiovascular diseases. Our aim was to evaluate role LRP8, particular from immune cells, inflammation. Methods LRP8 +/+ −/− mice (on B6;129S background) were infused with angiotensin II (AngII, 1 mg/kg/day 7 28 day)...