A5044212481- Atherosclerosis and Cardiovascular Diseases
- Inflammatory mediators and NSAID effects
- Peroxisome Proliferator-Activated Receptors
- Fatty Acid Research and Health
- Immune cells in cancer
- Antiplatelet Therapy and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Eicosanoids and Hypertension Pharmacology
- Cholesterol and Lipid Metabolism
- Cell Adhesion Molecules Research
- Estrogen and related hormone effects
- Cardiovascular Disease and Adiposity
- Extracellular vesicles in disease
- Diabetes Treatment and Management
- MicroRNA in disease regulation
- Adenosine and Purinergic Signaling
- Macrophage Migration Inhibitory Factor
- Protein Hydrolysis and Bioactive Peptides
- Lipoproteins and Cardiovascular Health
- Nuclear Receptors and Signaling
- Cancer, Lipids, and Metabolism
- Cerebrovascular and Carotid Artery Diseases
- Pregnancy and preeclampsia studies
- Circular RNAs in diseases
- NF-κB Signaling Pathways
University College Dublin
2013-2025
St. Vincent's University Hospital
2019
Conway School of Landscape Design
2016
Royal College of Surgeons in Ireland
2000-2004
University of Toronto
2003
Abstract Mesenchymal stem cells (MSCs) inhibit T‐cell activation and proliferation but their effects on individual T‐cell‐effector pathways memory versus naïve T remain unclear. MSC influence the differentiation of CD4 + toward Th17 phenotype was examined. exposed to Th17‐skewing conditions exhibited reduced CD25 IL‐17A expression following co‐culture. Inhibition production persisted upon re‐stimulation in absence MSCs. These were attenuated when cell–cell contact prevented. cultures from...
The formation of prostacyclin (PGI(2)), thromboxane (TX) A(2), and isoprostanes is markedly enhanced in atherosclerosis. We examined the relative contribution cyclooxygenase (COX)-1 -2 to generation these eicosanoids patients with atherosclerosis.The study population consisted 42 atherosclerosis who were undergoing surgical revascularization. COX-2 mRNA was detected areas but not normal blood vessel walls, there evidence COX-1 induction. use immunohistochemical studies localized...
The let-7 miRNA family plays a key role in modulating inflammatory responses. Vascular smooth muscle cell (SMC) proliferation and endothelial (EC) dysfunction are critical the pathogenesis of atherosclerosis, including setting diabetes. Here we report that levels decreased diabetic human carotid plaques model diabetes-associated ApoE-/- mouse. In vitro platelet-derived growth factor (PDGF)- tumor necrosis factor-α (TNF-α)-induced vascular SMC EC activation was associated with reduced...
Atherosclerosis is an inflammatory disease caused by endothelial injury, lipid deposition, and oxidative stress. This progressive can be converted into acute clinical event plaque rupture thrombosis. In the context of atherosclerosis, underlying cause myocardial infarction stroke, macrophages uniquely possess a dual functionality, regulating accumulation metabolism sustaining chronic response, two most well-documented pathways associated with pathogenesis disease. Macrophages are...
Increasing evidence points to the fact that defects in resolution of inflammatory pathways predisposes individuals development chronic diseases, including diabetic complications such as accelerated atherosclerosis. The inflammation is dynamically regulated by production endogenous modulators inflammation, lipoxin A4 (LXA4). Here, we explored therapeutic potential LXA4 and a synthetic LX analog (Benzo-LXA4) modulate streptozotocin-induced ApoE−/− mouse human carotid plaque tissue ex vivo....
Milk-derived bioactive peptides retain many biological properties and have therapeutic effects in cardiovascular disorders such as atherosclerosis. Under inflammatory conditions the expression of endothelial cells adhesion molecules is induced, increasing monocyte to human vessel wall, a critical step pathogenesis In present work we explored milk-derived on phenotype their adherence cells. Treatment with hydrolysate inhibited production proteins MCP-1 IL-8 VCAM-1, ICAM-1 E-selectin. Milk...
Macrophages play a pivotal role in atherosclerotic plaque development. Recent evidence has suggested the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can attenuate pro-inflammatory responses macrophages. We hypothesized that liraglutide could limit atherosclerosis progression vivo via modulation of inflammatory response. Human THP-1 macrophages and bone marrow-derived macrophages, from both wild-type C57BL/6 (WT) apolipoprotein E null mice (ApoE−/−) were used to...
Abstract Extracellular vesicles (EVs) are emerging as key players in different stages of atherosclerosis. Here we provide evidence that EVs released by mixed aggregates monocytes and platelets response to TNF‐α display pro‐inflammatory actions on endothelial cells atherosclerotic plaques. Tempering platelet activation with Iloprost, Aspirin or a P2Y 12 inhibitor impacted quantity phenotype EV produced. Proteomics from activated alone the presence Iloprost revealed distinct composition,...
Cyclooxygenase (COX) activity is induced in human atherosclerosis, and the products formed may modify disease directly or through an effect on platelets. We examined role of COX-1 -2 platelet vessel wall interactions development atherosclerosis a murine model.Apolipoprotein E-deficient (apoE-/-) mice fed 1% cholesterol diet were treated with selective inhibitor (SC-560), COX-2 (SC-236), vehicle. Urinary prostacyclin thromboxane metabolites (2,3-dinor-6-keto-PGF1alpha 2,3-dinor-TXB2)...
Background— Pulmonary hypertension induced by chronic hypoxia is characterized thickening of pulmonary artery walls, elevated vascular resistance, and right-heart failure. Prostacyclin analogues reduce pressures in this condition; raising the possibility that cycloxygenase-2 (COX-2) modulates response vasculature to hypoxia. Methods Results— Sprague-Dawley rats which was hypobaric for 14 days were treated concurrently with selective COX-2 inhibitor SC236 or vehicle. Mean arterial pressure...
<title>Abstract</title> Defective clearance of apoptotic cells (efferocytosis) by macrophages is a key driver atherosclerotic plaque necrosis which associated with adverse clinical outcomes such as myocardial infarction and stroke. The mechanistic basis defective efferocytosis in not well understood. We show that hyperlipidemia the consequent accumulation lipids triggers endoplasmic reticulum stress directly impairs efferocytosis. Mechanistically, we demonstrate lipid accumulation-induced...
Conjugated linoleic acid (CLA) induces regression of preestablished atherosclerosis in the ApoE–/– mouse. Understanding mechanisms involved may help identifying novel pathways associated with human disease. Animals were administered a 1% cholesterol diet for 12 wk, CLA supplementation from wk 8 to 12. mice fed only employed as controls. Transcriptomic analysis mouse aorta showed that many components IL-10 signaling pathway modified during CLA-induced regression. Real-time PCR and Western...
Conjugated linoleic acid (CLA) has the unique property of inducing regression pre‐established murine atherosclerosis. Understanding mechanism(s) involved may help identify endogenous pathways that reverse human Here, we provide evidence CLA inhibits foam cell formation via regulation nuclear receptor coactivator, peroxisome proliferator‐activated (PPAR)‐γ coactivator (PGC)‐1α, and macrophage PGC‐1α plays a role in atheroprotection vivo . was identified as hub gene within cluster aorta apoE...
We have shown that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (Lir) inhibits development of early atherosclerosis in vivo by modulating immune cell function. hypothesized Lir could attenuate pre-established disease monocyte or macrophage phenotype to induce atheroprotective responses. Human atherosclerotic plaques obtained postendarterectomy and human peripheral blood macrophages were treated ex with Lir. In parallel, apolipoprotein E–deficient (ApoE<sup>−/−</sup>)...
Atherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization inflammation are governed microRNAs (miR) that regulate the expression of proteins cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize miR-155-5p (miR-155) regulated conjugated linoleic acid (CLA), pro-resolving mediator which induces regression atherosclerosis vivo. In parallel, as extracellular vesicles (EVs) their miR...
Inflammation driven by pro-inflammatory cytokines is a new therapeutic target in coronary disease. Few data exist on the association of key upstream and post-stroke recurrence. In prospective cohort study, we investigated between pivotal cytokines, high-sensitivity C-reactive protein (hsCRP) one-year outcomes.BIO-STROKETIA multi-center study non-severe ischemic stroke (modified Rankin score ≤ 3) transient attack. Controls were patients with symptoms attending attack clinics non-ischemic...
Dysregulation of inflammatory responses is a hallmark multiple diseases such as atherosclerosis and rheumatoid arthritis. As constitutively active transcription factors, NR4A nuclear receptors function to control the magnitude in chronic disease can be protective or pathogenic. Within this study, we demonstrate that TLR4 stimulation using endotoxin lipopolysaccharide (LPS) rapidly enhances NR4A1-3 expression human murine, primary immortalized myeloid cells with concomitant gene protein...