A5046534291- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- Advanced Fluorescence Microscopy Techniques
- ATP Synthase and ATPases Research
- Ion channel regulation and function
- Connexins and lens biology
- Photoreceptor and optogenetics research
- Circadian rhythm and melatonin
- Cardiovascular Health and Disease Prevention
- Metabolism and Genetic Disorders
- Eicosanoids and Hypertension Pharmacology
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Cancer, Hypoxia, and Metabolism
- Heart Rate Variability and Autonomic Control
- Sodium Intake and Health
- Genetic Neurodegenerative Diseases
- Calcium signaling and nucleotide metabolism
- Metabolomics and Mass Spectrometry Studies
- Optical Coherence Tomography Applications
- Signaling Pathways in Disease
- Ocular and Laser Science Research
- Optical Imaging and Spectroscopy Techniques
University of Strathclyde
2015-2024
Karolinska Institutet
2022
University of Liverpool
2014
Durham University
2012
University of Salford
1990
Key points The endothelium plays a pivotal role in the vascular response to chemical and mechanical stimuli. is exquisitely sensitive ACh, although physiological significance of ACh‐induced activation unknown. In present study, we investigated mechanisms flow‐mediated endothelial calcium signalling. Our data establish that responses arise from autocrine action non‐neuronal ACh released by endothelium. Abstract Circulating blood generates frictional forces (shear stress) on walls vessels....
Endothelial cells line all blood vessels and are critical regulators of vascular tone. In hypertension, disruption endothelial function alters the release endothelial-derived vasoactive factors results in increased Although vasodilators occurs a Ca2+-dependent manner, little is known on how Ca2+ signaling altered hypertension. A key element to control tone signals at specialized regions (myoendothelial projections) that connect smooth muscle cells. This work describes operation this pathway...
The TRPV4 ion channels are Ca2+ permeable, non-selective cation that mediate large, but highly localized, signals in the endothelium. mechanisms permit localized changes to evoke cell-wide activity incompletely understood. Here, we tested hypothesis TRPV4-mediated influx activates release from internal stores generate widespread effects.Ca2+ large numbers (~100) of endothelial cells intact arteries were imaged and analysed separately.Responses channel agonist GSK1016790A heterogeneous across...
Abstract Arteries and veins are lined by nonproliferating endothelial cells that play a critical role in regulating blood flow. Endothelial also regulate tissue perfusion, metabolite exchange, thrombosis. It is thought rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, metabolism has mainly been studied the context proliferative cells, little known about energy production within fully formed...
Objective— Mitochondria are widely described as being highly dynamic and adaptable organelles, their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart smooth muscle, mitochondria stationary rigidly structured. The significance the differences mitochondrial behavior physiological function cells unclear was studied single myocytes intact resistance-sized cerebral arteries. We hypothesized that dynamics controlled by proliferative status...
Covalent immobilisation of a low cost electrocatalyst leads to an enhanced rate photoelectron transfer from light absorbing semiconductor.
Agonist-mediated signaling by the endothelium controls virtually all vascular functions. Because of large diversity agonists, each with varying concentrations, background noise often obscures individual cellular signals. How distinguishes low-level fluctuations from and decodes integrates physiologically relevant information remains unclear. Here, we recorded changes in intracellular Ca(2+) concentrations response to acetylcholine areas encompassing hundreds endothelial cells inside intact...
Clusters of endothelial cells exhibit distinct sensitivities to different agonists and cooperate process multiple signals.
BackgroundObesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, stroke. Impaired endothelial function occurs in the earliest stages of obesity underlies vascular alterations that give rise to disease. However, mechanisms link weight gain dysfunction are ill-defined. Increasing evidence suggests cells not population uniform but highly heterogeneous organized communicating multicellular network controls function.PurposeTo investigate...
Significance The endothelium is the single layer of cells lining all blood vessels and acts as a central control hub to regulate multiple cardiovascular functions in response hundreds physiological stimuli. detection various stimuli distributed spatially separated sites across endothelium. Distributed sensing difficult reconcile with requirement for coordinated cell activity large regions Here, we show that resolves issue by using network scale-free small-world properties. organization...
VasoTracker 2 is an open-source platform for studying blood vessel dynamics, featuring versatile diameter-tracking software and complementary low-cost hardware components. This system surpasses existing tools through accessible, high-resolution analysis across multiple imaging modalities, enabling comprehensive assessment of vascular dynamics in both real-time pre-recorded experiments. Advanced algorithms enable multi-point diameter tracking branched vessels, automated pressure-response...
Increased pressure suppresses endothelial control of vascular tone but it remains uncertain (1) how is sensed by the endothelium and (2) response inhibited. This study used a novel imaging method to large numbers cells in arteries that were physiological configuration held at normal blood pressures. suppressed IP3 -mediated Ca(2+) signals. Pressure modulated cell shape. The changes shape may alter signals modulating diffusive environment for near receptors. Endothelial pressure-dependent...
Pressure myography, one of the most commonly used techniques in vascular research, measures diameter isolated, pressurized arteries to assess functional activity smooth muscle and endothelial cells. Despite widespread adoption this technique for assessing function, there are only a small number commercial systems these expensive. Here, we introduce complete, open source pressure myograph system analysis software, VasoTracker, that can be set-up approximately 10% cost alternatives. We report...
BACKGROUND: Endothelial cell TRPV4 (transient receptor potential vanilloid 4) channels provide a control point that is pivotal in regulating blood vessel diameter by mediating the Ca 2+ -dependent release of endothelial-derived vasoactive factors. In hypertension, TRPV4-mediated vascular function disrupted, but underlying mechanisms and precise physiological consequences remain controversial. METHODS: Here, using comprehensive array methodologies, endothelial channel was examined intact...
Background and Purpose Coordinated endothelial control of cardiovascular function is proposed to occur by cell communication via gap junctions connexins. To study intercellular communication, the pharmacological agents carbenoxolone (CBX) 18β‐glycyrrhetinic acid (18βGA) are used widely as connexin inhibitors junction blockers. Experimental Approach We investigated effects CBX 18βGA on Ca 2+ waves, evoked inositol 1,4,5‐trisphosphate (IP 3 ) in endothelium intact mesenteric resistance...
Hydrogen peroxide (H2O2) is a mitochondrial-derived reactive oxygen species (ROS) that regulates vascular signalling transduction, vasocontraction and vasodilation. Although the physiological role of ROS in endothelial cells acknowledged, mechanisms underlying H2O2 regulation native, fully-differentiated unresolved. In present study, effects on Ca2+ were investigated endothelium intact rat mesenteric arteries. Spontaneous local signals acetylcholine evoked increases inhibited by H2O2....
Background and Purpose Ca 2+ influx via TRPV4 channels triggers release from the IP 3 ‐sensitive internal store to generate repetitive oscillations. Although mitochondria are acknowledged regulators of ‐mediated release, how TRPV4‐mediated signals regulated by is unknown. We show that depolarised switch signalling relying on ‐induced at receptors being independent instead mediated ATP pannexins. Experimental Approach TRPV4‐evoked were individually examined in hundreds cells endothelium rat...
The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co-ordination centre that controls wide range vascular functions including regulation pressure and flow. To co-ordinate activities, communication among required for tissue level responses to emerge. While significant form occurs by propagation signals between cells, mechanism in intact endothelium unresolved.
Abstract Protease‐activated receptor‐1 & ‐2 (PAR1 and PAR2) are expressed widely in cardiovascular tissues including endothelial smooth muscle cells. PAR1 PAR2 may regulate blood pressure via changes vascular contraction or relaxation mediated by Ca 2+ signaling, but the mechanisms incompletely understood. By using single‐cell imaging across hundreds of cells intact vessels, we explored PAR‐mediated regulation vessel function activators. We show that activation evoked multicellular waves...