Ingrid Fleming
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View article: The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells Open
Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characterized changes in the endothelial cell m…
View article: Cystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation
Cystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation Open
Endothelial metabolism underpins tissue regeneration, health, and longevity. We uncover a nuclear oxidative catabolic pathway linking cystine to gene regulation. Cells preparing to proliferate upregulate the SLC7A11 transporter to import c…
View article: Immunomodulatory endothelial cells contribute to T cell recruitment and activation through antigen presentation on MHC class II
Immunomodulatory endothelial cells contribute to T cell recruitment and activation through antigen presentation on MHC class II Open
Aims A subset of endothelial cells referred to as immunomodulatory endothelial cells (IMEC) has been proposed to regulate T cell responses in atherosclerosis, but their phenotype and function remain poorly understood. Here, we characterize…
View article: Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase
Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase Open
The bifunctional soluble epoxide hydrolase (sEH) represents a promising target for inflammation-related diseases. Although potent inhibitors targeting each domain are available, sEH-PROTACs offer the unique ability to simultaneously block …
View article: The Ever‐Expanding Influence of the Endothelial Nitric Oxide Synthase
The Ever‐Expanding Influence of the Endothelial Nitric Oxide Synthase Open
Nitric oxide (NO) generated by the endothelial NO synthase (eNOS) plays an essential role in the maintenance of vascular homeostasis and the prevention of vascular inflammation. There are a myriad of mechanisms that regulate the activity o…
View article: A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling
A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling Open
Fatty acid metabolites, produced by cytochrome P450 enzymes and soluble epoxide hydrolase (sEH), regulate inflammation. Here, we report that the transforming growth factor β (TGF-β)-induced polarization of macrophages to a pro-resolving ph…
View article: The transaminase-ω-amidase pathway is a redox switch in glutamine metabolism that generates α-ketoglutarate
The transaminase-ω-amidase pathway is a redox switch in glutamine metabolism that generates α-ketoglutarate Open
Summary Oxidative stress is caused by short-lived molecules and metabolic changes belong to the fastest cellular responses. Here we studied how the endothelial cell metabolome reacts to acute oxidative challenges (menadione or H 2 O 2 ) to…
View article: Pericyte-to-Endothelial Cell Communication via Tunneling Nanotubes Is Disrupted by a Diol of Docosahexaenoic Acid
Pericyte-to-Endothelial Cell Communication via Tunneling Nanotubes Is Disrupted by a Diol of Docosahexaenoic Acid Open
The pericyte coverage of microvessels is altered in metabolic diseases, but the mechanisms regulating pericyte–endothelial cell communication remain unclear. This study investigated the formation and function of pericyte tunneling nanotube…
View article: Metabolic alterations drive inflammatory phenotypes in CHIP-associated heart failure
Metabolic alterations drive inflammatory phenotypes in CHIP-associated heart failure Open
Summary Mutations in DNA methyltransferase 3 alpha (DNMT3A) are the most frequent driver of clonal hematopoiesis of indeterminate potential (CHIP), and associated with higher risk of cardiovascular disease and pro-inflammatory activation o…
View article: The European Society of Cardiology Working Group on Coronary Pathophysiology and Microcirculation
The European Society of Cardiology Working Group on Coronary Pathophysiology and Microcirculation Open
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View article: Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation
Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation Open
Aims The cytokine interleukin-6 (IL-6) plays a central role in the inflammation cascade as well as cardiovascular disease progression. Since myeloid cells are a primary source of IL-6 formation, we aimed to generate a mouse model to study …
View article: Nuclear eNOS interacts with and<i>S</i>-nitrosates ADAR1 to modulate type I interferon signaling and endothelial function
Nuclear eNOS interacts with and<i>S</i>-nitrosates ADAR1 to modulate type I interferon signaling and endothelial function Open
Background Nitric oxide (NO) generated by the endothelial NO synthase (eNOS) regulates vascular tone and endothelial homeostasis to counteract vascular inflammation. Most eNOS is localized at the cell membrane or in the Golgi apparatus, bu…
View article: Nuclear eNOS interacts with and S-nitrosates ADAR1 to modulate endothelial gene expression
Nuclear eNOS interacts with and S-nitrosates ADAR1 to modulate endothelial gene expression Open
Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Collaborative Research Centre (CRC 1366); Chinese Scholarship Council (CSC) Introduction and Aim Nitric oxide (NO) generated by the endothelial NO syntha…
View article: High-throughput proteo-genomic identification of functional endothelial cell microproteins encoded by non-canonical small open reading frames
High-throughput proteo-genomic identification of functional endothelial cell microproteins encoded by non-canonical small open reading frames Open
Detecting microproteins (miPs) translated from small open reading frames (smORFs) by mass spectrometry poses major challenges. Here we report a high-throughput proteo-genomic pipeline that identified a large number of intracellular and ext…
View article: Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3
Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3 Open
Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes …
View article: Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis
Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis Open
BACKGROUND: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac p…
View article: Role of the soluble epoxide hydrolase in keratinocyte proliferation and sensitivity of skin to inflammatory stimuli
Role of the soluble epoxide hydrolase in keratinocyte proliferation and sensitivity of skin to inflammatory stimuli Open
The lipid content of skin plays a determinant role in its barrier function with a particularly important role attributed to linoleic acid and its derivatives. Here we explored the consequences of interfering with the soluble epoxide hydrol…
View article: Health position paper and redox perspectives - Disease burden by transportation noise
Health position paper and redox perspectives - Disease burden by transportation noise Open
Transportation noise is a ubiquitous urban exposure. In 2018, the World Health Organization concluded that chronic exposure to road traffic noise is a risk factor for ischemic heart disease. In contrast, they concluded that the quality of …
View article: Age-dependent RGS5 loss in pericytes induces cardiac dysfunction and fibrosis in the heart
Age-dependent RGS5 loss in pericytes induces cardiac dysfunction and fibrosis in the heart Open
Background Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although ageing is one of the main risk factors for cardiovascular disease, the consequences of ageing on cardiac …
View article: Impaired Detoxification of Trans, Trans‐2,4‐Decadienal, an Oxidation Product from Omega‐6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease
Impaired Detoxification of Trans, Trans‐2,4‐Decadienal, an Oxidation Product from Omega‐6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease Open
Omega‐6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega‐6 fatty acids to an oxidative environment results in the generation of a highly re…
View article: MyD88 in myeloid cells promotes angiotensin II-induced vascular inflammation and is associated with all-cause mortality and incident heart failure in humans with arterial hypertension
MyD88 in myeloid cells promotes angiotensin II-induced vascular inflammation and is associated with all-cause mortality and incident heart failure in humans with arterial hypertension Open
Background Angiotensin II (AngII) causes hypertension and promotes vascular accumulation of inflammatory cells. We aimed to determine how myeloid factor of differentiation 88 (MyD88) contributes to vascular dysfunction and arterial hyperte…
View article: Inhibition of fatty acid oxidation enables heart regeneration in adult mice
Inhibition of fatty acid oxidation enables heart regeneration in adult mice Open
Postnatal maturation of cardiomyocytes is characterized by a metabolic switch from glycolysis to fatty acid oxidation, chromatin reconfiguration and exit from the cell cycle, instating a barrier for adult heart regeneration 1,2 . Here, to …
View article: Epoxyeicosatrienoic Acids Prevent Cardiac Dysfunction in Viral Myocarditis via Interferon Type I Signaling
Epoxyeicosatrienoic Acids Prevent Cardiac Dysfunction in Viral Myocarditis via Interferon Type I Signaling Open
Myocarditis is a challenging inflammatory disease of the heart, and better understanding of its pathogenesis is needed to develop specific drug therapies. Epoxyeicosatrienoic acids (EETs), active molecules synthesized by CYP (cytochrome P4…
View article: Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers
Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers Open
Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutan…
View article: Cardiovascular Functions of Ena/VASP Proteins: Past, Present and Beyond
Cardiovascular Functions of Ena/VASP Proteins: Past, Present and Beyond Open
Actin binding proteins are of crucial importance for the spatiotemporal regulation of actin cytoskeletal dynamics, thereby mediating a tremendous range of cellular processes. Since their initial discovery more than 30 years ago, the enable…
View article: Inhibition of proline-rich-tyrosine kinase 2 restores cardioprotection by remote ischemic preconditioning in type 2 diabetes mellitus
Inhibition of proline-rich-tyrosine kinase 2 restores cardioprotection by remote ischemic preconditioning in type 2 diabetes mellitus Open
Background Endothelial function and cardioprotection through remote ischemic preconditioning (rIPC) are severely impaired in type 2 diabetes mellitus (T2DM). Proline-rich tyrosine kinase 2 (Pyk2), a downstream target of the insulin recepto…