Menno P.J. de Winther
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View article: A CROP-seq screen of histone modifying enzymes reveals histone demethylase Kdm5c regulates inflammatory macrophage activation
A CROP-seq screen of histone modifying enzymes reveals histone demethylase Kdm5c regulates inflammatory macrophage activation Open
Background Macrophages adopt activation states along a spectrum from pro- to anti-inflammatory, enabling appropriate responses to pathogens and environmental cues. Dysregulated inflammatory macrophage activation contributes to diseases inc…
View article: Human monocyte inflammation in patients with Lp(a) or atherosclerotic cardiovascular disease is not accompanied by changes in chromatin accessibility in circulating classical monocytes
Human monocyte inflammation in patients with Lp(a) or atherosclerotic cardiovascular disease is not accompanied by changes in chromatin accessibility in circulating classical monocytes Open
While subjects with high Lp(a) levels showed enhanced monocyte inflammation, no differences in chromatin accessibility were detected. This suggests that the pro-inflammatory signature of Lp(a) and ASCVD on monocytes is regulated at a level…
View article: Female-biased vascular smooth muscle cell gene regulatory networks predict MYH9 as a key regulator of fibrous plaque phenotype
Female-biased vascular smooth muscle cell gene regulatory networks predict MYH9 as a key regulator of fibrous plaque phenotype Open
Atherosclerosis, a chronic inflammatory condition driving coronary artery disease (CAD), manifests in two primary plaque types: unstable atheromatous plaques and stable fibrous plaques. While significant research has focused on atheromatou…
View article: Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Roadmap for alleviating the manifestations of ageing in the cardiovascular system Open
View article: Endothelial-to-Mesenchymal Transition Gene Signature Derived from Single-Cell Transcriptomics of Human Atherosclerotic Tissue Associates with Stable Plaque Histological Characteristics
Endothelial-to-Mesenchymal Transition Gene Signature Derived from Single-Cell Transcriptomics of Human Atherosclerotic Tissue Associates with Stable Plaque Histological Characteristics Open
View article: Novel insights into the dynamic function of PRC2 in innate immunity
Novel insights into the dynamic function of PRC2 in innate immunity Open
The polycomb repressive complex 2 (PRC2) is an established therapeutic target in cancer. PRC2 catalyzes methylation of histone H3 at lysine 27 (H3K27me3) and is known for maintaining eukaryote cell identity. Recent discoveries show that mo…
View article: The human milk oligosaccharide 3′sialyllactose reduces low-grade inflammation and atherosclerosis development in mice
The human milk oligosaccharide 3′sialyllactose reduces low-grade inflammation and atherosclerosis development in mice Open
Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjuga…
View article: Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages
Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages Open
Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcripto…
View article: Clonal Hematopoiesis Is Associated With Long‐Term Adverse Outcomes Following Cardiac Surgery
Clonal Hematopoiesis Is Associated With Long‐Term Adverse Outcomes Following Cardiac Surgery Open
Background Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short‐term inflammation‐mediated outcomes after cardiac surgery. The impact of CH on l…
View article: Sexual dimorphism in atherosclerotic plaques of aged Ldlr−/− mice
Sexual dimorphism in atherosclerotic plaques of aged Ldlr−/− mice Open
View article: Human atherosclerotic plaque macrophages associate with clinical presentation and follow diverse lineage differentiation routes
Human atherosclerotic plaque macrophages associate with clinical presentation and follow diverse lineage differentiation routes Open
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Research Council Veni grant. Netherlands Heart Foundation Atherosclerosis is characterized by inflammation and lipid ac…
View article: Untangling the inflammatory responses of liver x receptor (LXR) activation in human macrophages
Untangling the inflammatory responses of liver x receptor (LXR) activation in human macrophages Open
Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Rembrandt Institute for Cardiovascular Science (grant 2022) The regulation of cholesterol and fatty acid homeostasis is essential and the Live…
View article: Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans
Atherosclerotic Plaque Epigenetic Age Acceleration Predicts a Poor Prognosis and Is Associated With Endothelial-to-Mesenchymal Transition in Humans Open
BACKGROUND: Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events. METHODS: Whole-g…
View article: Infiltrative classical monocyte-derived and<i>SPP1</i>lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis
Infiltrative classical monocyte-derived and<i>SPP1</i>lipid-associated macrophages mediate inflammation and fibrosis in ANCA-associated glomerulonephritis Open
Background Kidney macrophage infiltration is a histological hallmark of vasculitic lesions and is strongly linked to disease activity in anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN). The precise mechani…
View article: T cell specific deletion of Casitas B lineage lymphoma-b reduces atherosclerosis, but increases plaque T cell infiltration and systemic T cell activation
T cell specific deletion of Casitas B lineage lymphoma-b reduces atherosclerosis, but increases plaque T cell infiltration and systemic T cell activation Open
Introduction Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall, and the underlying cause of the majority of cardiovascular diseases. Recent advances in high-parametric immunophenotyping of immune cells indicate th…
View article: Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation
Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation Open
BACKGROUND: Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that addition…
View article: Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques
Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques Open
View article: Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages
Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages Open
Immunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites durin…
View article: Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification Open
View article: Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 Open
Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus …
View article: Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques
Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques Open
BACKGROUND: Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women…
View article: Single-cell profiling reveals age-associated immune cells in atherosclerosis
Single-cell profiling reveals age-associated immune cells in atherosclerosis Open
View article: Single-cell T-cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T-cells
Single-cell T-cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T-cells Open
View article: EZH2 inhibition reduces macrophage inflammatory responses in atherosclerosis
EZH2 inhibition reduces macrophage inflammatory responses in atherosclerosis Open
View article: Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI
Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI Open
View article: Single-cell profiling reveals age-associated immunity in atherosclerosis
Single-cell profiling reveals age-associated immunity in atherosclerosis Open
Aims Aging is a dominant driver of atherosclerosis and induces a series of immunological alterations, called immunosenescence. Given the demographic shift towards elderly, elucidating the unknown impact of aging on the immunological landsc…
View article: The regulatory landscape of macrophage interferon signaling in inflammation
The regulatory landscape of macrophage interferon signaling in inflammation Open
The pervasive role of the innate immune system is established by interferons. Emerging research shows an underappreciated ability of macrophages to regulate and propagate interferon responses in infectious and autoinflammatory disease stat…
View article: The Epigenetic Reader Protein SP140 Regulates Dendritic Cell Activation, Maturation and Tolerogenic Potential
The Epigenetic Reader Protein SP140 Regulates Dendritic Cell Activation, Maturation and Tolerogenic Potential Open
SP140 is an epigenetic reader protein expressed predominantly in immune cells. GWAS studies have shown an association between SP140 single nucleotide polymorphisms (SNPs) and diverse autoimmune and inflammatory diseases, suggesting a possi…
View article: Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis
Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis Open
Background Atherosclerosis is the underlying cause of many cardiovascular diseases, such as myocardial infarction or stroke. B cells, and their production of pro- and anti-atherogenic antibodies, play an important role in atherosclerosis. …
View article: Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation
Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation Open