A5028598758- Cardiac Fibrosis and Remodeling
- Angiogenesis and VEGF in Cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Congenital heart defects research
- Circular RNAs in diseases
- Geophysics and Gravity Measurements
- Arctic and Antarctic ice dynamics
- Coronary Interventions and Diagnostics
- Mesenchymal stem cell research
- Nerve injury and regeneration
- Synthetic Aperture Radar (SAR) Applications and Techniques
- Tissue Engineering and Regenerative Medicine
- Signaling Pathways in Disease
- Cardiovascular Function and Risk Factors
- Cardiac Ischemia and Reperfusion
- Advanced SAR Imaging Techniques
- Cryospheric studies and observations
- Oceanographic and Atmospheric Processes
- Nuclear Receptors and Signaling
- Ocean Waves and Remote Sensing
- Peripheral Artery Disease Management
- IL-33, ST2, and ILC Pathways
- Cardiac Structural Anomalies and Repair
- Bone Metabolism and Diseases
Sanofi (France)
2019-2024
University of Edinburgh
2015-2022
The Queen's Medical Research Institute
2017-2022
Queen's Medical Centre
2018-2020
University of Bristol
2008-2020
British Heart Foundation
2010-2020
European Space Research Institute
2011-2020
European Organisation for the Exploitation of Meteorological Satellites
2020
NIHR Bristol Cardiovascular Biomedical Research Unit
2006-2019
Serco (United Kingdom)
2019
Background— Diabetes mellitus impairs endothelial cell (EC) function and postischemic reparative neovascularization by molecular mechanisms that are not fully understood. microRNAs negatively regulate the expression of target genes mainly interaction in their 3′ untranslated region. Methods Results— We found microRNA-503 (miR-503) ECs is upregulated culture conditions mimicking diabetes (high D-glucose) ischemia-associated starvation (low growth factors). Under normal conditions,...
A better understanding of the pathways that regulate regeneration coronary vasculature is fundamental importance for advancement strategies to treat patients with heart disease. Here, we aimed investigate origin and clonal dynamics endothelial cells (ECs) associated neovascularization in adult mouse following myocardial infarction (MI). Furthermore, sought define murine cardiac heterogeneity characterize transcriptional profiles pro-angiogenic resident ECs heart, at single-cell resolution.
We evaluated the healing potential of human fetal aorta-derived CD133 + progenitor cells and their conditioned medium (CD133 CCM) in a new model ischemic diabetic ulcer. Streptozotocin-induced mice underwent bilateral limb ischemia wounding. One wound was covered with collagen containing 2×10 4 or − vehicle. The contralateral wound, only collagen, served as control. Fetal expressed high levels wingless ( Wnt ) genes, which were downregulated following differentiation into along upregulation...
Circulating proangiogenic cells (PACs) support postischemic neovascularization. Cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms that are not fully known. We hypothesize a role for microRNAs (miRs). miRs currently investigated as potential diagnostic prognostic biomarkers.
Nerve growth factor (NGF) promotes angiogenesis and cardiomyocyte survival, which are both desirable for postinfarction myocardial healing. Nonetheless, the NGF potential cardiac repair has never been investigated.To define expression localization of its high-affinity receptor TrkA (tropomyosin-related A) in human infarcted heart to investigate roles endogenous engineered using a mouse model infarction (MI).Immunostaining was performed on samples from humans deceased MI or unrelated...
To develop an embryoid body-free directed differentiation protocol for the rapid generation of functional vascular endothelial cells derived from human embryonic stem (hESCs) and to assess system microRNA regulation angiogenesis.The production defined cell lineages hESCs is a critical requirement evaluating their potential in regenerative medicine. We developed feeder- serum-free protocol. Directed revealed loss pluripotency markers progressive induction mRNA protein expression (including...
Myocardial infarction (MI) is the leading cause of death worldwide. MicroRNAs regulate expression their target genes, thus mediating a plethora pathophysiological functions. Recently, miRNA-24 emerged as an important but controversial miRNA involved in post-MI responses. Here, we aimed at clarifying effect adenovirus-mediate intra-myocardial delivery decoy for mouse MI model and to investigate impact inhibition on angiogenesis cardiovascular apoptosis. After induction, was lower peri-infarct...
Rationale: Optimization of cell therapy for cardiac repair may require the association different populations with complementary activities. Objective: Compare reparative potential saphenous vein–derived pericytes (SVPs) that stem cells (CSCs) in a model myocardial infarction, and investigate whether combined transplantation provides further improvements. Methods Results: SVPs CSCs were isolated from vein leftovers coronary artery bypass graft surgery discarded atrial specimens transplanted...
Abstract The communication between vascular endothelial cells (ECs) and pericytes in the microvasculature is fundamental for growth homeostasis; however, these processes are disrupted by diabetes. Here we show that modulation of p75 NTR expression ECs exposed to high glucose activates transcription miR-503, which negatively affects pericyte function. NF-κB bind miR-503 promoter upregulate ECs. further induces activation Rho kinase shedding microparticles carrying transfer from pericytes....
The hallmarks of diabetic cardiomyopathy are cardiac oxidative stress, intramyocardial inflammation, fibrosis, and apoptosis. Given the antioxidative, antiinflammatory, antiapoptotic potential high-density lipoprotein (HDL), we evaluated hypothesis that increased HDL via gene transfer (GT) with human apolipoprotein (apo) A-I, principal HDL, may reduce development cardiomyopathy.Intravenous GT 3x10(12) particles/kg E1E3E4-deleted vector Ad.hapoA-I, expressing apoA-I, or Ad.Null, containing no...
Pain triggers a homeostatic alarm reaction to injury. It remains unknown, however, whether nociceptive signaling activated by ischemia is relevant for progenitor cells (PC) release from bone marrow. To this end, we investigated the role of neuropeptide substance P (SP) and cognate neurokinin 1 (NK1) nociceptor in PC activation angiogenesis during mice human subjects.The mouse marrow contains sensory fibers that express SP. Moreover, SP-induced migration provides enrichment NK1 promote...
The increasing incidence of diabetes mellitus will result in a new epidemic heart failure unless novel treatments able to halt diabetic cardiomyopathy early its course are introduced. This study aimed determine whether the activity Akt/Pim-1 signaling pathway is altered at critical stages and supplementation with vitamin B1 analog benfotiamine (BFT) helps sustain above prosurvival mechanism, thereby preserving cardiomyocyte viability function.Untreated streptozotocin-induced type 1 or...
MicroRNAs (miRNAs) are short noncoding RNAs, which post-transcriptionally regulate gene expression. miRNAs transcribed as precursors and matured to active forms by a series of enzymes, including Dicer. important in governing cell differentiation, development, disease. We have recently developed feeder- serum-free protocol for direct derivation endothelial cells (ECs) from human embryonic stem (hESCs) provided evidence increases angiogenesis-associated (miR-126 -210) during the process....
Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation TGF-β signaling leads to pathological conditions in vasculature, causing cardiovascular disease and fibrotic disorders. The pathway critical endothelial-to-mesenchymal transition (EndMT), but a gap remains our understanding related endothelium. This study applied gain- loss-of function approach an vivo model skin wound healing demonstrate that miR-148b regulates has key...
In ST-segment elevation myocardial infarction of both patients and mice, there was a decline in blood eosinophil count, with activated eosinophils recruited to the infarct zone. Eosinophil deficiency resulted attenuated anti-inflammatory macrophage polarization, enhanced inflammation, increased scar size, deterioration structure function. Adverse cardiac remodeling setting prevented by interleukin-4 therapy.
Abstract Aims Long non-coding RNAs (lncRNAs) play functional roles in physiology and disease, yet understanding of their contribution to endothelial cell (EC) function is incomplete. We identified lncRNAs regulated during EC differentiation investigated the role LINC00961 its encoded micropeptide, small regulatory polypeptide amino acid response (SPAAR), function. Methods results Deep sequencing human embryonic stem ECs was combined with Encyclopedia DNA Elements (ENCODE) RNA-seq data from...
Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary from human mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion EGF/bFGF, which signal through ERK1/2, or exposure MEK inhibitor PD0325901. Differentiated became more proangiogenic, responsive vasoactive agents, insensitive chemoattractants. RNA...
Angiotensin II (Ang II), acting through its G protein-coupled AT1 receptor (AT1), contributes to the precocious heart senescence typical of patients with hypertension, atherosclerosis, and diabetes. was suggested transactivate an intracellular signaling controlled by growth factors their tyrosin-kinase receptors. In cultured vascular smooth muscle cells, this downstream mechanism comprises p66Shc adaptor protein, previously recognized play a role in cell death. The aim present study 2-fold:...
Diabetes impairs endothelial function and reparative neovascularization. The p75 receptor of neurotrophins (p75 NTR ), which is scarcely present in healthy cells (ECs), becomes strongly expressed by capillary ECs after induction peripheral ischemia type-1 diabetic mice. Here, we show that gene transfer-induced expression the survival, proliferation, migration, adhesion capacities cultured progenitor (EPCs) inhibits angiogenesis vitro. Moreover, intramuscular delivery neovascularization blood...
Phosphoinositide 3-kinase (PI3K)gamma is expressed in hematopoietic cells, endothelial cells (ECs), and cardiomyocytes regulates different cellular functions relevant to inflammation, tissue remodeling cicatrization. Recently, PI3Kgamma inhibitors have been indicated for the treatment of chronic inflammatory/autoimmune diseases atherosclerosis.We aimed determine contribution angiogenic capacity ECs effect inhibition on healing myocardial infarction (MI).Human umbilical were treated with a...
There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins. We investigated role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation subsequent II–mediated signaling under diabetic conditions. To investigate effect HDL AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks transfer, 1.9-fold ( P =0.001) increase cholesterol associated with 4.7-fold...
Notch signaling regulates vascular development. However, the implication of ligand Delta-like 4 (Dll4) in postischemic angiogenesis remains unclear.We investigated role Dll4/Notch reparative using a mouse model ischemia.We found Dll4 weakly expressed microvascular endothelial cells normoperfused muscles. Conversely, is upregulated following ischemia and localized at forefront sprouting capillaries. We analyzed effect inhibiting endogenous by intramuscular injection an adenovirus encoding...