A5066292590- MicroRNA in disease regulation
- Virus-based gene therapy research
- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Dialysis and Renal Disease Management
- Pulmonary Hypertension Research and Treatments
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Extracellular vesicles in disease
- Birth, Development, and Health
- Renal and Vascular Pathologies
- Viral gastroenteritis research and epidemiology
- Biomarkers in Disease Mechanisms
- CAR-T cell therapy research
- Viral Infections and Immunology Research
- Dementia and Cognitive Impairment Research
- Cardiovascular Disease and Adiposity
- Telomeres, Telomerase, and Senescence
- Adenosine and Purinergic Signaling
- Eosinophilic Esophagitis
- Monoclonal and Polyclonal Antibodies Research
- IL-33, ST2, and ILC Pathways
University of Edinburgh
2016-2025
The Queen's Medical Research Institute
2016-2025
British Heart Foundation
2007-2024
University of Glasgow
2006-2017
British Heart Foundation Centre for Cardiovascular Science
2016
Jagiellonian University
2016
Queen's Medical Centre
2016
Heart Foundation
2010
Memorial Sloan Kettering Cancer Center
2010
Medical Research Council
2006
Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which novel IL-1–like cytokine signals via ST2, can reduce atherosclerosis development in ApoE−/− mice on high-fat diet. IL-33 ST2 are present normal atherosclerotic humans. Although control PBS-treated developed severe inflamed plaques aortic sinus, lesion was profoundly reduced IL-33–treated animals. also markedly increased levels IL-4, -5, -13, but...
MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds genes. The regulation miRNAs in lung during development pulmonary arterial hypertension (PAH) unknown.We screened profiles longitudinal and crossover design PAH caused by chronic hypoxia or monocrotaline rats. We identified reduced expression Dicer, involved processing, onset after...
Significance Statement The innate immune system is central to injury and repair in the kidney, but heterogeneity of myeloid cell subsets behind these processes unknown. Complementary technologies—including bulk tissue transcriptomics, integrated droplet– plate-based single-cell RNA sequencing, paired blood exchange—resolved a murine model reversible unilateral ureteric obstruction, creating atlas. identified novel could be targeted ameliorate or enhance repair, including an Arg1+ monocyte...
Renal tubulointerstitial fibrosis is the common end point of progressive renal disease. MicroRNA (miR)-214 and miR-21 are upregulated in models injury, but function miR-214 this setting effect its manipulation remain unknown. We assessed inhibiting an animal model fibrosis. In mice, genetic deletion significantly attenuated interstitial induced by unilateral ureteral obstruction (UUO). Treatment wild-type mice with anti-miR directed against (anti-miR-214) before UUO resulted similar...
Rationale: Despite increasing understanding of the prognostic importance vascular stiffening linked to perivascular fibrosis in hypertension, molecular and cellular regulation this process is poorly understood. Objectives: To study functional role microRNA-214 (miR-214) induction endothelial dysfunction driving stiffening. Methods Results: Out 381 miRs screened tissues response Ang II (angiotensin II)-mediated miR-214 showed highest (8-fold, P =0.0001). MiR-214 was pronounced circulating T...
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides first layer of immunological defense within the abdomen. Here, we investigated mechanisms mediate capture during peritonitis. Single-cell RNA sequencing spatial analysis omental stromal cells revealed surface FALCs were covered by CXCL1+ mesothelial cells, which termed FALC cover cells. Blockade CXCL1 inhibited recruitment aggregation neutrophils at...
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Virus-mediated gene delivery is restricted by the infectivity profile of chosen vector. Targeting vascular endothelium via systemic has been attempted using peptides isolated in vitro (using either phage or vector display) and implicit reliance on target receptor expression vivo. This limited application since endothelial cells vivo differ vastly profiles because existence complex "zip codes" We therefore tested whether display combined with adeno-associated virus (AAV) capsid modifications...
The renin-angiotensin system regulates cardiovascular physiology via angiotensin II engaging the type 1 or 2 receptors. Classic actions are receptor mediated, whereas may counteract activity. Angiotensin-converting enzyme metabolizes to angiotensin-(1-7) and I angiotensin-(1-9). Angiotensin-(1-7) antagonizes Mas. Angiotensin-(1-9) was shown recently block cardiomyocyte hypertrophy receptor. Here, we investigated in vivo effects of angiotensin-(1-9) (100 ng/kg per minute) with without...
Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodeling. However, the molecular mechanisms that govern this remain largely unknown, including contribution of long noncoding RNAs (lncRNAs). Objectives: To investigate role lncRNAs EndMT and their relevance to Methods Results: study vitro, primary endothelial cells were treated with transforming growth factor-β2 interleukin-1β. Single-cell bulk RNA-seq...
Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney heart. Glioma-associated oncogene 1 expressing (Gli1
Fibrosis pathophysiology is critically regulated by Smad 2– and 3–mediated transforming growth factor-β (TGF-β) signaling. Disintegrin metalloproteases (Adam) can manipulate the signaling environment, however, role regulation of ADAMs in renal fibrosis remain unclear. TGF-β stimulation cells results a significant up-regulation Adams 10, 17, 12, 19. The selective Smad2/3 inhibitor SB 525334 reversed these TGF-β–induced changes. In vivo, using ureteral obstruction to model fibrosis, we...
BackgroundHyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney (CKD), although the mechanism this poorly understood. We investigated effects of sustained exposure to a high-phosphate environment on endothelial function cellular and preclinical models, as well human subjects.
Abstract Background Excessive TGF-β signalling has been shown to underlie pulmonary hypertension (PAH). Human artery smooth muscle cells (HPASMCs) can release extracellular vesicles (EVs) but their contents and significance have not yet studied. Here, we aimed analyse the biological relevance of HPASMC-EVs transport human arterial endothelial (HPAECs), as well potential alteration these under pathological conditions. Methods We used low-input RNA-Seq RNA cargoes sorted into released basal...
Dyslipidemia is a main driver of cardiovascular diseases. The ability macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism key development new treatments. Here, we investigated how adipose tissue regulate post-prandial cholesterol transport. Single-cell RNA sequencing protected bone marrow chimeras demonstrated that ingestion led specific transcriptional activation population resident...
Progressive fibrosis and maladaptive organ repair result in significant morbidity millions of premature deaths annually. Senescent cells accumulate with aging after injury are implicated fibrosis, but the mechanisms by which senescence influences poorly understood. Using 2 murine models repair, we show that obstructive generated senescent epithelia, persisted resolution original injury, promoted ongoing impeded adaptive repair. Depletion ABT-263 reduced reversed ureteric obstruction renal...
Edinburgh Kidney, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, United Kingdom Correspondence: Dr. Laura Denby, email: [email protected] See related article, "ATP-Gated P2X7-Ion Channel on Kidney-Resident Natural Killer T Cells and Memory in Intrarenal Inflammation," pages 602–613.