Calum Wilson

Calum Wilson
University of Strathclyde · Strathclyde Institute of Pharmacy and Biomedical Sciences

Doctor of Engineering

About

73
Publications
6,612
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657
Citations
Citations since 2017
50 Research Items
601 Citations
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140
2017201820192020202120222023020406080100120140

Publications

Publications (73)
Article
Full-text available
Key points The endothelium plays a pivotal role in the vascular response to chemical and mechanical stimuli. The endothelium is exquisitely sensitive to ACh, although the physiological significance of ACh‐induced activation of the endothelium is unknown. In the present study, we investigated the mechanisms of flow‐mediated endothelial calcium signa...
Article
Full-text available
Endothelial cells are reported to be glycolytic and to minimally rely on mitochondria for ATP generation. Rather than providing energy, mitochondria in endothelial cells may act as signaling organelles that control cytosolic Ca2+ signaling or modify reactive oxygen species (ROS). To control Ca2+ signaling, these organelles are often observed close...
Article
Full-text available
Pressure myography, one of the most commonly used techniques in vascular research, measures the diameter of isolated, pressurized arteries to assess the functional activity of smooth muscle and endothelial cells. Despite the widespread adoption of this technique for assessing vascular function, there are only a small number of commercial systems an...
Article
Full-text available
Endothelial cells line all blood vessels and are critical regulators of vascular tone. In hypertension, disruption of endothelial function alters the release of endothelial-derived vasoactive factors and results in increased vascular tone. Although the release of endothelial-derived vasodilators occurs in a Ca2+-dependent manner, little is known on...
Article
Full-text available
Background Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfuncti...
Article
Full-text available
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of...
Article
Full-text available
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 to hundreds of physiological stimuli. The detection of various physiological stimuli is distributed in spatially separated sites across the endothelium. Distributed sensing is...
Article
Protease activated receptors (PARs), a subfamily of G-protein-coupled receptors, are activated by cleavage of its extracellular domains. Four mammalian PAR members have been identified (PAR1-4). PAR1 is the thrombin receptor, while PAR2 is activated physiologically by peptides or N-terminal proteolytic cleavage. The resulting cleaved N-termini acts...
Article
The endothelium is the innermost layer of all blood vessels and it controls a host of cardiovascular functions including vascular contractility, hemostasis, inflammation and the exchange of nutrients and waste products between circulating blood and tissue. The importance of the endothelium is clear since changes in the behaviour of this single laye...
Article
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis to fuel each of these energy-demanding processes. However, endothelia...
Article
The endothelium is a sheet of highly-specialised cells that line every blood vessel. Endothelial cells detect, integrate and respond to information from numerous signals, passing this information to neighbouring endothelial cells via intercellular communication to coordinate vascular contractility, inflammation and exchange of products between the...
Article
Full-text available
Background and purpose: Ca2+ influx via TRPV4 triggers Ca2+ release from the IP3 -sensitive internal store to generate repetitive oscillations. While mitochondria are acknowledged regulators of IP3 -mediated Ca2+ release, how TRPV4-mediated Ca2+ signals are regulated by mitochondria is unknown. We show that depolarised mitochondria switch TRPV4 si...
Preprint
Full-text available
Arteries and veins are lined by non-proliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis to fuel each of these energy-demanding processes. However, endothelia...
Conference Paper
Full-text available
Mitochondria are significant regulators of intracellular Ca2+ signalling in the vascular endothelium. Depolarization of the mitochondrial membrane potential (Δψm) inhibits IP3-mediated Ca2+ release and may regulate Ca2+ influx across the plasma membrane. However, precisely how Ca2+ influx is regulated by mitochondria in the endothelium is unknown....
Article
Full-text available
Photouncaging delivers compounds with high spatial and temporal control to induce or inhibit biological processes but the released compounds may diffuse out. We here demonstrate that sulfonate anions can be...
Article
Full-text available
Background and purpose: Coordinated endothelial control of cardiovascular function is proposed to occur by endothelial cell communication via gap junctions and connexins. To study intercellular communication, the pharmacological agents carbenoxolone (CBX) and 18β glycyrrhetinic acid (18βGA) are used widely as connexin inhibitors and gap junction b...
Article
Full-text available
Pyruvate is oxidized to acetyl‐CoA by pyruvate dehydrogenase which is localized in the mitochondrial matrix. The mitochondrial pyruvate carrier (MPC) is a hetero-oligomer composed of SLC54 family members (MPC1 and MPC2). The MPC is expressed in the inner mitochondrial membrane and involved in the import of pyruvate into mitochondria [1, 5]. Ubiquit...
Preprint
Full-text available
Rationale Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations giving rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction a...
Conference Paper
Side viewing GRIN imaging systems may be used to investigate calcium signalling events in the vascular endothelium. However, curvature of the artery wall and inherent field curvature in the GRIN system serve to degrade image field of view and resolution. In this work we quantify these aberrations, with an aim to introduce corrections into the imagi...
Article
Full-text available
Background and purpose: FK506 and rapamycin are modulators of FK-binding proteins (FKBP) that are used to suppress immune function after organ and hematopoietic stem cell transplantations. The drugs share the unwanted side-effect of evoking hypertension that is associated with reduced endothelial function and nitric oxide production. The underlyin...
Article
Full-text available
Rapid imaging of multiple focal planes without sample movement may be achieved through remote refocusing, where imaging is carried out in a plane conjugate to the sample plane. The technique is ideally suited to studying the endothelial and smooth muscle cell layers of blood vessels. These are intrinsically linked through rapid communication and mu...
Article
Full-text available
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 is acknowledged, the mechanisms underlying H2O2 regulation of signalling in native, fully-differentiated endothelial cells is...
Article
Full-text available
Background and purpose: Transient receptor potential vanilloid 4 (TRPV4) channels are Ca2+ -permeable, nonselective cation channels that mediate large, but highly-localized, Ca2+ signals in the endothelium. The mechanisms that permit highly-localized Ca2+ changes to evoke cell-wide activity are incompletely understood. Here we tested the hypothesi...
Article
Full-text available
The endothelium is the single layer of cells lining all blood vessels, and it is a remarkable cardiovascular control centre. Each endothelial cell has only a small number (on average six) of interconnected neighbours. Yet this arrangement produces a large repertoire of behaviours, capable of controlling numerous cardiovascular functions in a flexib...
Article
Full-text available
Blood flow, blood clotting, angiogenesis, vascular permeability, and vascular remodeling are each controlled by a large number of variable, noisy, and interacting chemical inputs to the vascular endothelium. The endothelium processes the entirety of the chemical composition to which the cardiovascular system is exposed, carrying out sophisticated c...
Poster
Calcium Imaging Across Large Areas of Intact Vascular Endothelium Reveals Stimulus-Specific Sensory Cells
Article
Full-text available
The endothelium is the single layer of cells that lines the entire cardiovascular system and regulates vascular tone and blood–tissue exchange, recruits blood cells, modulates blood clotting, and determines the formation of new blood vessels. To control each function, the endothelium uses a remarkable sensory capability to continuously monitor vani...
Article
Full-text available
Aging is the summation of many subtle changes which result in altered cardiovascular function. Impaired endothelial function underlies several of these changes and precipitates plaque development in larger arteries. The endothelium transduces chemical and mechanical signals into changes in the cytoplasmic calcium concentration to control vascular f...
Data
Movie S9. Flow‐mediated Ca2+ signalling in mesenteric artery endothelia is abolished by atropine. The movie shows two sequential experimental recordings obtained from a single en face carotid artery preparation. The first recording shows a control response to flow (flow was initiated at t = 17 s). The second recording shows a response to flow in th...
Data
Movie S3. Exogenous ACh augments flow‐mediated Ca2+ signalling. Ca2+ signalling was examined in a cut‐opened (en face) preparation of an carotid artery in which the endothelium was loaded with the Ca2+ indicator, Cal‐520/AM. The timescale of the Ca2+ imaging recording is indicated at the top right of the movie panel. Flow (1.5 ml min−1) was initiat...
Data
Movie S4. Flow‐mediated Ca2+ signals originate in distinct subcellular locations. The movie shows active Ca2+ wavefronts (green; obtained by sequential subtraction of raw imaging data) overlaid on a single Ca2+ image (grey; obtained by averaging raw imaging data). The movie begins at the onset of flow, and is first played before being rewound and p...
Data
Movie S7. Prolonged activation of TRPV4 channels induces large‐scale propagating Ca2+ waves in en face carotid artery preparations. The movie shows active Ca2+ wavefronts (green; obtained by sequential subtraction of raw imaging data) overlaid on a single Ca2+ image (grey; obtained by averaging raw imaging data). Scale bar = 50 μm.
Data
Movie S1. Flow‐mediated Ca2+ signals in the endothelium of a carotid artery. Ca2+ signalling was examined in a cut‐opened (en face) preparation of an artery in which the endothelium was loaded with the Ca2+ indicator, Cal‐520/AM. The movie shows a raw 5 min long Ca2+ imaging recording (left; Played at 10× speed) and baseline‐corrected Ca2+ signals...
Data
Movie S6. Activation of TRPV4 channels induces local Ca2+ signals followed by global Ca2+ increases in en face carotid artery preparations. The movie begins just prior to the onset of activation (t = 20 s) by the specific TRPV4 agonist, GSK1016790A (30 nm). Scale bar = 50 μm.
Data
Movie S8. Flow‐mediated Ca2+ signalling in carotid artery endothelia is abolished by atropine. The movie shows three sequential experimental recordings obtained from a single en face carotid artery preparation. The first recording shows a control response to flow (flow was initiated at t = 15 s). The second recording shows a control response during...
Data
Movie S2. Flow‐mediated Ca2+ signals in the endothelium of a second‐order mesenteric artery. Ca2+ signalling was examined in a cut‐opened (en face) preparation of an artery in which the endothelium was loaded with the Ca2+ indicator, Cal‐520/AM. The timescale of the Ca2+ imaging recording is indicated at the top right of the movie panel. Flow (1.5...
Data
Movies S5. Spontaneous Ca2+ signals in the endothelium of a mesenteric artery. Ca2+ signalling was examined in a cut‐opened (en face) preparation of an artery in which the endothelium was loaded with the Ca2+ indicator, Cal‐520/AM. The movie shows a raw 60 s long Ca2+ imaging recording (left) and a binary image highlighting locations of spontaneous...
Chapter
In smooth muscle, Ca2+ release from the internal store into the cytoplasm occurs via inositol trisphosphate (IP3R) and ryanodine receptors (RyR). The internal Ca2+ stores containing IP3R and RyR may be arranged as multiple separate compartments with various IP3R and RyR arrangements, or there may be a single structure containing both receptors. The...
Article
Full-text available
Agonist-mediated signaling by the endothelium controls virtually all vascular functions. Because of the large diversity of agonists, each with varying concentrations, background noise often obscures individual cellular signals. How the endothelium distinguishes low-level fluctuations from noise and decodes and integrates physiologically relevant in...
Data
Movie S2. ACh activated IP3‐evoked endothelial Ca2+ signals which were recorded from inside pressurized arteries. At 60 mmHg, ACh caused an initial burst of Ca2+ increases that propagate as waves. As ACh‐evoked Ca2+ waves expanded collision between adjacent cells occurred and wave annihilation occurred. As a result of multiple waves progressions an...
Data
Movie S3. ACh activated IP3‐evoked Ca2+ signals were significantly attenuated as the artery transmural pressure increased from 60 mmHg to 110 mmHg to 160 mmHg. After each application of ACh the bath solution was washed with >20 times the bath volume, and the artery was allowed to re‐equilibrate for 20 minutes before the next pressure change and ACh...
Data
Movie S1. ACh‐evoked endothelial Ca2+ signals in a pressurised (60 mmHg) rat carotid artery. Activation of IP3‐evoked endothelial Ca2+ signals, by bath application of ACh (100 μM), causes a rise in cytoplasmic Ca2+ concentration in the majority of cells across the field of view. The movie is composed of raw data, to which a 5‐frame rolling average...
Article
Full-text available
Key points Increased pressure suppresses endothelial control of vascular tone but it remains uncertain (1) how pressure is sensed by the endothelium and (2) how the vascular response is inhibited. This study used a novel imaging method to study large numbers of endothelial cells in arteries that were in a physiological configuration and held at nor...
Article
Full-text available
The diversity of mitochondrial arrangements, which arise from the organelle being static or moving, or fusing and dividing in a dynamically reshaping network, is only beginning to be appreciated. While significant progress has been made in understanding the proteins that reorganise mitochondria, the physiological significance of the various arrange...
Article
Full-text available
Mitochondrial Ca(2+) uptake contributes important feedback controls to limit the time course of Ca(2+) signals. Mitochondria regulate cytosolic [Ca(2+) ] over an exceptional breath of concentrations (~200 nM to > 10 μM) to provide a wide dynamic range in the control of Ca(2+) signals. Ca(2+) uptake is achieved by passing the ion down the electroche...
Article
Objective: Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to th...

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