A5081452014- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Immune cells in cancer
- Immune Response and Inflammation
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protease and Inhibitor Mechanisms
- Cerebrovascular and Carotid Artery Diseases
- Lipoproteins and Cardiovascular Health
- Cardiovascular Disease and Adiposity
- Cell Adhesion Molecules Research
- Single-cell and spatial transcriptomics
- Acute Myocardial Infarction Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Systemic Lupus Erythematosus Research
- NF-κB Signaling Pathways
- Congenital Heart Disease Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cardiovascular Health and Disease Prevention
- Anesthesia and Neurotoxicity Research
- Cytokine Signaling Pathways and Interactions
- Pulmonary Hypertension Research and Treatments
- Inflammasome and immune disorders
University of Oxford
2016-2025
Nuffield Orthopaedic Centre
2015-2025
Hospital Israelita Albert Einstein
2008-2025
Kennedy Center
2007-2024
Institute of Rheumatology
2007-2024
Munich Cluster for Systems Neurology
2024
Sociedade Brasileira de Cardiologia
2023
Policlinico Tor Vergata
2020
John Radcliffe Hospital
2018
Imperial College London
2005-2017
Background Elevated plasma levels of C-reactive protein have been found in the majority patients with unstable angina. The evidence elevated acute-phase proteins angina is line a growing body that suggests inflammation plays role this syndrome and an indirect sign increased production interleukin-6, which major determinant acute-phase–protein by liver. However, angina, there no direct proof played interleukin-6. Methods Results We measured interleukin-6 38 at time their admission to coronary...
Abstract Objective: Although postoperative cognitive dysfunction (POCD) often complicates recovery from major surgery, the pathogenic mechanisms remain unknown. We explored whether systemic inflammation, in response to surgical trauma, triggers hippocampal inflammation and subsequent memory impairment, a mouse model of orthopedic surgery. Methods: C57BL/6J, knock out (lacking interleukin [IL]‐1 receptor, IL‐1R −/− ) wild type mice underwent surgery tibia under general anesthesia. Separate...
Cognitive decline following surgery in older individuals is a major clinical problem of uncertain mechanism; similar cognitive also follows severe infection, chemotherapy, or trauma and currently without effective therapy. A variety mechanisms have been proposed, exploring the role inflammation, we recently reported IL-1β hippocampus after mice with postoperative dysfunction. Here, show that TNF-α upstream IL-1 provokes its production brain. Peripheral blockade able to limit release prevent...
Abstract Objective: Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand mechanisms whereby brain is targeted by how this be resolved. Methods: C57BL/6J, Ccr2 RFP/+ Cx3cr1 GFP/+ , Ikk F/F mice LysM‐Cre/Ikk underwent stabilized tibial fracture operation under analgesia general anesthesia. Separate...
Blood vessels are exposed to multiple mechanical forces that exerted on the vessel wall (radial, circumferential and longitudinal forces) or endothelial surface (shear stress). The stresses strains experienced by arteries influence initiation of atherosclerotic lesions, which develop at regions complex blood flow. In addition, plaque progression eventually rupture is influenced a interaction between biological factors—mechanical regulate cellular molecular composition plaques and,...
Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed neutrophils emergency granulopoiesis drove a maladaptive during sepsis. We generated whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune identified populations immunosuppressive mature immature neutrophils. In co-culture, CD66b+ inhibited proliferation activation CD4+ T...
Abstract The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse outcomes. Atherosclerosis, a major underlying cause of disease, conceptualized as lipid-driven in which macrophages play nonredundant role. However, evidence emerging so far from single-cell atlases suggests dichotomy between lipid-associated inflammatory macrophage states. Here, we present an inclusive reference atlas human intraplaque cell communities. Combining RNA...
Nuclear factor κB (NF-κB) activation has been observed in human atherosclerotic plaques and is enhanced unstable coronary plaques, but whether such a protective or pathophysiological role remains to be determined. We addressed this question by developing short-term culture system of cells isolated from tissue, allowing efficient gene transfer directly investigate signaling pathways atherosclerosis. found that NF-κB activated these activity involves p65, p50, c-Rel not p52 RelB. This can...
Vascular endothelial growth factor (VEGF) is the most cell-specific angiogenic characterised to date, and it produced by a variety of cell types. In macrophages, VEGF has been shown be upregulated inflammatory mediator lipopolysaccharide (LPS) engagement CD40 ligand (CD40L). Because LPS CD40L activate nuclear factor-kappaB (NF-kappaB) in monocytes, we investigated this study whether production when stimulated with either or CD40L, NF-kappaB-dependent. We used adenoviral constructs...
The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide (LPS) challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 (HMGB-1), microglial activation, dysfunction. Disabling the interleukin (IL)-1 signaling pathway sufficient to reduce inflammation ameliorate disability.Endotoxemia was induced in wild-type IL-1R-/- mice by intra peritoneal injection E. Coli LPS (1...
Background— We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques. Methods and Results— A chip-based robotic nanoelectrospray platform interfaced triple quadrupole spectrometer was adapted analyze lipids in tissue sections extracts from human endarterectomy specimens by shotgun lipidomics. Eighteen scans for different classes plus additional fatty acids resulted the detection 150 species 9 which 24 were detected...
The critical role of Toll-like receptors (TLRs) in mammalian host defense has been extensively explored recent years. capacity about 10 TLRs to recognize conserved patterns on many bacterial and viral pathogens is remarkable. With so few receptors, cross-reactivity with self-tissue components often occurs. Previous studies have frequently assigned detrimental roles TLRs, particular TLR2 TLR4, immune cardiovascular disease. Using human murine systems, we investigated the consequence TLR3...
Background— Inflammation and matrix degradation are the hallmarks of high-risk atherosclerosis that leads to myocardial infarction stroke. Toll-like receptors (TLRs), key players in innate immunity, upregulated atherosclerotic lesions, but their functional role human is unknown. We explored effects blocking TLR-2, TLR-4, myeloid differentiation primary response gene 88 (MyD88), a signaling adaptor shared by most TLRs interleukin-1 receptor (IL-1R), an vitro model atherosclerosis. Methods...
Atherosclerosis is characterized by the abundant infiltration of myeloid cells starting at early stages disease. Myeloid are key players in vascular immunity during atherogenesis. However, subsets have eluded resolution due to shared marker expression and atypical heterogeneity tissues. We applied high-dimensionality mass cytometry study cell atherosclerosis. Apolipoprotein E-deficient (ApoE−/−) mice were fed a chow or high fat (western) diet for 12 weeks. Single-cell aortic preparations...
Abstract Innate inflammation is a hallmark of both experimental and human atherosclerosis. The predominant innate immune cell in the atherosclerotic plaque monocyte-macrophage. behaviour this type within heterogeneous depends on recruitment diverse monocyte subsets. Furthermore, microenvironment offers polarisation activation signals which impact phenotype. Microenvironmental are sensed through pattern recognition receptors, including toll-like NOD-like receptors thus dictating macrophage...
The identification of patients with high-risk atherosclerotic plaques prior to the manifestation clinical events remains challenging. Recent findings question histology- and imaging-based definitions "vulnerable plaque," necessitating an improved approach for predicting onset symptoms.We performed a proteomics comparison vascular extracellular matrix associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus asymptomatic identify protein signature plaques....
Summary Monocytes as cells of the innate immunity are prominently involved in development atherosclerotic lesions. The heterogeneity blood monocytes has widely been acknowledged by accumulating experimental and clinical data suggesting a differential, subset-specific contribution corresponding subpopulations to pathology cardiovascular other diseases. This document re-evaluates current nomenclature summarises key findings on monocyte subset biology propose consensus statement about...
GPR84 is a member of the metabolic G protein-coupled receptor family, and its expression has been described predominantly in immune cells. activation involved inflammatory response but mechanisms by which it modulates inflammation have incompletely described. In this study, we investigated expression, function macrophages to establish role during response. We observed that murine tissues increased endotoxemia, hyperglycemia hypercholesterolemia. Ex vivo studies revealed mRNA LPS other...