Maria Febbraio

Maria Febbraio
University of Alberta | UAlberta · School of Dentistry

PhD

About

228
Publications
25,546
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21,004
Citations
Citations since 2017
37 Research Items
7703 Citations
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201720182019202020212022202302004006008001,0001,2001,400
201720182019202020212022202302004006008001,0001,2001,400
201720182019202020212022202302004006008001,0001,2001,400

Publications

Publications (228)
Article
Periodontitis, one of the most common inflammatory conditions, and the leading cause of adult tooth loss, has been identified as an independent risk factor for cardiovascular disease (CVD). Long-term studies in edentulous patients with a history of periodontitis showed persistence of increased CVD risk for years after edentulism, suggesting that cl...
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Clearance of dying cells by efferocytosis is necessary for cardiac repair after myocardial infarction (MI). Recent reports have suggested a protective role for vascular endothelial growth factor C (VEGFC) during acute cardiac lymphangiogenesis post MI. Here we report that defective efferocytosis by macrophages after experimental MI leads to a reduc...
Article
Purpose: This study introduces a standardized 2-plane approach using 8 landmarks to assess alveolar bone levels in mice using micro-computed tomography. Materials and methods: Bone level differences were described as distance from the cemento-enamel junction (CEJ) to alveolar bone crest (ABC) and as percentages of vertical bone height and vertic...
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High-fat Western diets contribute to tissue dysregulation of fatty acid and glucose intake, resulting in obesity and insulin resistance and their sequelae, including atherosclerosis. New therapies are desperately needed to interrupt this epidemic. The significant idea driving this research is that the understudied regulation of fatty acid entry int...
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There is substantial evidence in support of an association between periodontitis and cardiovascular disease. The most important open question related to this association is causality. This article revisits the question of causality by reviewing intervention studies and systematic reviews and meta analyses published in the last 3 years. Where are we...
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The mechanism controlling long-chain fatty acid (LCFA) mobilization from adipose tissue (AT) is not well understood. Here, we investigated how the LCFA transporter CD36 regulates this process. By using tissue-specific knockout mouse models, we show that CD36 in both adipocytes and endothelial cells mediates both LCFA deposition into and release fro...
Article
Objective To determine if AP5055 drug, an inhibitor of CD36, prevents the increase in Porphyromonas gingivalis (P. gingivalis) mediated atherosclerosis in low-density lipoprotein receptor knockout (LDLR KO) mice by targeting CD36. Methods Male LDLR KO mice were infected with P. gingivalis by oral lavage to induce periodontal disease and fed a west...
Article
CD36 is a multifunctional transmembrane glycoprotein abundantly expressed in several cell types. Recent studies have identified CD36 in circulation (cCD36) in several chronic inflammatory diseases, including type 2 diabetes and chronic kidney disease, and proposed cCD36 to be a biomarker of disease activity. Whether cCD36 is present in hyperlipidem...
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Fatty acid translocase (CD36) is a scavenger receptor with multiple ligands and diverse physiological actions. We recently reported that alcohol-induced hepatic retinoid mobilization is impaired in Cd36−/− mice, leading us to hypothesize that CD36 has a novel role in hepatic vitamin A mobilization. Given the central role of the liver in systemic vi...
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Thrombospondin-1 (TSP-1) is released by platelets upon activation and can promote platelet activation, but its role in haemostasis in vivo is unclear. We show that TSP-1 is a critical mediator of haemostasis that promotes platelet activation by modulating inhibitory cAMP signaling. Genetic deletion of TSP-1 did not affect platelet activation in vit...
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Background and aims Scavenger receptor class B member 3, also known as cluster of differentiation-36 (CD36) receptor, is involved in the uptake and accumulation of modified lipoprotein in macrophages, driving atherosclerosis progression. Azapeptide analogs of growth hormone-releasing peptide-6 (GHRP-6) have been developed as selective CD36 ligands...
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Objectives: The aim of this study was to investigate whether a peptide-based coating can prevent the adhesion of Porphyromonas gingivalis, a key human pathogen associated with periodontitis and peri-implantitis. Background: Nonsurgical and surgical interventions have been used for the treatment of peri-implantitis; however, the effectiveness of...
Article
Aim: First, to determine the feasibility of using the low density lipoprotein receptor knockout (LDLR KO) mouse model to study apical periodontitis (AP). Second, to investigate the causal relationship between AP and atherosclerosis. It was hypothesized that it would be feasible to induce AP and atherosclerosis in LDLR KO mice and find a difference...
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Background: CD36, a member of the class B scavenger receptor family, participates in Toll-like receptor signaling on mononuclear phagocytes (MP) and can promote sterile pathogenic inflammation. We here analyzed the effect of CD36 deficiency on retinal inflammation and photoreceptor degeneration, the hallmarks of age-related macular degeneration (AM...
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Although it is established that fatty acid (FA) synthesis supports anabolic growth in cancer, the role of exogenous FA uptake remains elusive. Here we show that, during acquisition of resistance to HER2 inhibition, metabolic rewiring of breast cancer cells favors reliance on exogenous FA uptake over de novo FA synthesis. Through cDNA microarray ana...
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Loricrin downregulation has been associated with age‐related changes as well as inherited and inflammatory skin diseases. We hypothesize that changes in loricrin could be more related to altered barrier function and consequently disorders that affect epithelial cells, such as psoriasis, atopic dermatitis (AD), erythrokeratoderma, loricrin keratoder...
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Zusammenfassung Die Downregulation von Loricrin wurde mit alterungsbedingten Veränderungen, mit Genodermatosen und entzündlichen Hauterkrankungen assoziiert. Wir stellen die Hypothese auf, dass Veränderungen bei Loricrin eng mit einer veränderten Barrierefunktion verbunden sind und damit mit Störungen, welche die epithelialen Zellen betreffen wie P...
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In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mic...
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Prostacyclin (PGI2) controls platelet activation and thrombosis through a cyclic adenosine monophosphate (cAMP) signalling cascade. However, in patients with cardiovascular diseases this protective mechanism fails for reasons that are unclear. Using both pharmacological and genetic approaches we describe a mechanism by which oxidised low density li...
Article
Purpose of review: High-fat diets contribute to hyperlipidemia and dysregulated metabolism underlying insulin resistant states and cardiovascular diseases. Neointimal hyperplasia is a significant resulting morbidity. Increased fatty acid (FA) levels lead to dysfunctional endothelium, defined as activated, proinflammatory and prothrombotic. The pur...
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Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer...
Article
In healthy blood vessels, albumin crosses the endothelium to leave the circulation by transcytosis. However, little is known about the regulation of albumin transcytosis or how it differs in different tissues; its physiological purpose is also unclear. Using total internal reflection fluorescence microscopy, we quantified transcytosis of albumin ac...
Article
Objective— Dysregulated proliferation of vascular smooth muscle cells (VSMC) plays an essential role in neointimal hyperplasia. CD36 functions critically in atherogenesis and thrombosis. We hypothesize that CD36 regulates VSMC proliferation and contributes to the development of obstructive vascular diseases. Approach and Results— We found by immun...
Article
Synchrotron radiation X-ray fluorescence microscopy is frequently used to investigate the spatial distribution of elements within a wide range of samples. Interrogation of heterogeneous samples that contain large concentration ranges has the potential to produce image artefacts due to the profile of the X-ray beam. The presence of these artefacts a...
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Oxidized low-density lipoprotein (oxLDL) and associated oxidized phosphocholine-headgroup phospholipids (oxPCs) activate blood platelets through ligation of the scavenger receptor CD36. Previously, we found that oxLDL stimulated phosphorylation of phospholipase Cγ2 (PLCγ2). However, the functional relevance of PLCγ2 phosphorylation in oxLDL-mediate...
Article
CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-ac...
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In malaria, CD36 plays several roles including mediating parasite sequestration to host organs, phagocytic clearance of parasites and regulation of immunity. While the functions of CD36 in parasite sequestration and phagocytosis have been clearly defined, less is known about its role in malaria immunity. Here, to understand the function of CD36 in...
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Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently...
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Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αDβ2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration du...
Article
Atherosclerosis is a progressive narrowing of arteries that may lead to occlusion as a consequence of lipid deposition. It underlies coronary heart disease, as well as myocardial and cerebral infarctions. Recent attention has been directed towards the potential contribution of chronic inflammatory processes that may amplify vascular inflammation in...
Article
Previous studies have shown that loss of CD36 protects the heart from dysfunction induced by pressure overload in the presence of diet-induced insulin resistance and/or obesity. The beneficial effects of CD36 ablation in this context are mediated by preventing excessive cardiac fatty acid (FA) entry and reducing lipotoxic injury. However, whether o...
Article
Aggressive periodontal disease is an oral health mystery. Our current understanding of this disease is that specific bacteria invade the oral cavity and the host reacts with an inflammatory response leading to mass destruction of the alveolar bone. Aggressive periodontal disease is typically observed in a population under the age of 30 and occurs s...
Article
A systematic review was conducted to assess the association between apical periodontitis (AP) and cardiovascular disease (CVD). Studies published from the earliest date available until September 2015 were retrieved from the Medline, PubMed and Embase databases. The included studies reported the results from observational studies and assessed the li...
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CD36/FAT (fatty acid translocase) has been associated with human and murine non-alcoholic fatty liver disease (NAFLD), but it has been unclear if it is simply a marker or if it directly contributes to disease pathogenesis. Mice with hepatocyte-specific deletion of JAK2 (JAK2L) have increased circulating free fatty acids (FA), dramatically increased...
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Obesity and aging are associated with a state of chronic low-grade inflammation, initiated by nutrient overload. Although, fatty acids are inducers of inflammatory signaling in the liver, little is known regarding the mechanisms that link lipid availability at the cell membrane to inflammation.
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Staphylococcus aureus is the primary cause of skin and skin structure infections (SSSIs) in the United States. α-Hemolysin (Hla), a pore-forming toxin secreted by S. aureus and a major contributor to tissue necrosis, prompts recruitment of neutrophils critical for host defense against S. aureus infections. However, the failure to clear apoptotic ne...
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The removal of apoptotic cells is an innate function of tissue macrophages; however, its role in disease progression is unclear. The present study was designed to investigate the role of macrophage CD36, a recognized receptor of apoptotic cells and oxidized lipids, in two models of kidney injury: unilateral ureteral obstruction (UUO) and ischemia r...
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There is strong epidemiological association between periodontal disease and cardiovascular disease but underlying mechanisms remain ill-defined. Because the human periodontal disease pathogen, Porphyromonas gingivalis (Pg), interacts with innate immune receptors Toll-like Receptor (TLR) 2 and CD36/scavenger receptor-B2 (SR-B2), we studied how CD36/...
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Oxidised low-density lipoproteins (oxLDL) promote unregulated platelet activation in dyslipidemic disorders. While oxLDL stimulates activatory signalling, it is unclear how these events drive accelerated thrombosis. Here we describe a mechanism for oxLDL-mediated platelet hyperactivity that requires generation of reactive oxygen species (ROS). Unde...
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Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ). While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for...
Article
Epidemiological evidence strongly support a link between periodontal disease & cardiovascular disease, but the mechanism(s) remains poorly understood. Using the human periodontal disease associated bacteria, Porphyromonas gingivalis (Pg) as a model, we carried out studies in macrophages & low density lipoprotein receptor (LDLR) KO mice. Pg associat...
Article
Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial cells coordinately participates in the i...
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CD36 has been associated with obesity and diabetes in human liver diseases, however, its role in age-associated nonalcoholic fatty liver disease (NAFLD) is unknown. Therefore, liver biopsies were collected from individuals with histologically normal livers (n=30), and from patients diagnosed with simple steatosis (NAS; n=26). Patients were divided...
Article
Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36. Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression....
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Full-text available
Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a variety of ligands, including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight...
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Full-text available
Unresolved inflammatory response of macrophages plays a pivotal role in the pathogenesis of atherosclerosis. Previously we showed that ribosomal protein L13a-dependent translational silencing suppresses the synthesis of a cohort of inflammatory proteins in monocytes and macrophages. We also found that genetic abrogation of L13a expression in macrop...
Chapter
Stroke is a major leading cause of death and disability in the human population. The pathology of stroke-induced brain injury involves multifactorial pro-death processes. Among them, inflammation is an important contributor to stroke pathology as indicated by the close association between excessive inflammation and exacerbation of the disease proce...
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The scavenger receptor CD36 plays important roles in malaria, including the sequestration of parasite-infected erythrocytes in microvascular capillaries, control of parasitemia through phagocytic clearance by macrophages, and immunity. Although the role of CD36 in the parasite sequestration and clearance has been extensively studied, how and to wha...
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Objective: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and methods: Fat cell size and number were deter...
Article
Although pre-clinical evidence has suggested that partial inhibition of myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose oxidation for ATP production can prevent ischemia/reperfusion injury, controversy about this approach persists. For example, mice with germline deletion of the FA transporter CD36, exhibited either i...
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Aims: The CD36 selective ligand, EP 80317, features potent anti-atherosclerotic and hypocholesterolemic effects that are associated with an increase in macrophage cholesterol efflux through the activation of the peroxisome proliferator-activated receptor γ-liver X receptor α (LXRα)-ATP-binding cassette (ABC) transporter pathway. Cholesterol efflux...
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Aims: Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O₂⁻) inducing low-density lipoprotein (LDL) oxidation...
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Inhaled pollutants induce the release of vasoactive factors into the systemic circulation, but little information is available regarding the nature of these factors or their receptors. The pattern recognition receptor CD36 interacts with many damage-related circulating molecules, leading to activation of endothelial cells and promoting vascular inf...
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Background: Deciphering the molecular and cellular processes that govern macrophage foam cell formation is critical to understanding the basic mechanisms underlying atherosclerosis and other vascular pathologies. Methods and results: Here, we identify a pivotal role of plasminogen (Plg) in regulating foam cell formation. Deficiency of Plg inhibi...
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Dysregulation of renal tubular protein handling in proteinuria contributes to the development of chronic kidney disease. We investigated the role of CD36 as a novel candidate mediator of albumin binding and endocytosis in the kidney proximal tubule using both in vitro and in vivo approaches, and in nephrotic patient renal biopsy samples. In CD36-tr...
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The CD36 receptor plays an important role in facilitating fatty acid transport to the heart. The present study aimed to assess whether EP 80317, a selective synthetic peptide ligand of CD36, is cardioprotective in a murine model of myocardial ischaemia and reperfusion (MI/R) injury. Mice were pretreated with daily subcutaneous injections of EP 8031...
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Unlabelled: Although high mammographic density is considered one of the strongest risk factors for invasive breast cancer, the genes involved in modulating this clinical feature are unknown. Tissues of high mammographic density share key histologic features with stromal components within malignant lesions of tumor tissues, specifically low adipocy...
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Cell polarization is essential for migration and the exploratory function of leukocytes. However, the mechanism by which cells maintain polarity or how cells revert to the immobilized state by gaining cellular symmetry is not clear. Previously we showed that interaction between oxidized low-density lipoprotein (oxLDL) and CD36 inhibits macrophage m...
Article
Hyperlipidemia exacerbates ischemic stroke outcome and increases CD36 expression in the postischemic brain as well as in peripheral monocytes/macrophages. By exchanging bone marrow-derived cells between CD36-expressing and CD36-deficient mice, this study investigates the contribution of peripheral CD36 in comparison with that of brain CD36 to strok...