586 results on '"Smith, Alberto"'
Search Results
202. Reactive Oxygen Species in Venous Thrombosis.
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Gutmann, Clemens, Siow, Richard, Gwozdz, Adam M., Saha, Prakash, and Smith, Alberto
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VENOUS thrombosis ,REACTIVE oxygen species ,ERYTHROCYTES ,ANTIPHOSPHOLIPID syndrome ,MAST cells ,BLOOD coagulation ,CELLULAR control mechanisms ,OXIDATIVE stress - Abstract
Reactive oxygen species (ROS) have physiological roles as second messengers, but can also exert detrimental modifications on DNA, proteins and lipids if resulting from enhanced generation or reduced antioxidant defense (oxidative stress). Venous thrombus (DVT) formation and resolution are influenced by ROS through modulation of the coagulation, fibrinolysis, proteolysis and the complement system, as well as the regulation of effector cells such as platelets, endothelial cells, erythrocytes, neutrophils, mast cells, monocytes and fibroblasts. Many conditions that carry an elevated risk of venous thrombosis, such as the Antiphospholipid Syndrome, have alterations in their redox homeostasis. Dietary and pharmacological antioxidants can modulate several important processes involved in DVT formation, but their overall effect is unknown and there are no recommendations regarding their use. The development of novel antioxidant treatments that aim to abrogate the formation of DVT or promote its resolution will depend on the identification of targets that enable ROS modulation confined to their site of interest in order to prevent off-target effects on physiological redox mechanisms. Subgroups of patients with increased systemic oxidative stress might benefit from unspecific antioxidant treatment, but more clinical studies are needed to bring clarity to this issue. [ABSTRACT FROM AUTHOR]
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- 2020
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203. Neurohypophysial peptides in the human fetus: presence in pituitary extracts of immunoreactive arginine-vasotocin
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Smith, Alberto and McIntosh, Neil
- Abstract
A specific and sensitive radioimmunoassay was used to demonstrate the presence of arginine-vasotocin (AVT) in human fetal pituitary extracts. The mean pituitary contents of AVT in extracts of 70–101, 102–136 and 137–172 days gestation were 0·32, 0·8 and 8·1 ng/gland respectively. Combined high-pressure liquid chromatography (HPLC) and radioimmunoassay of pooled extracts at these gestational ages confirmed the presence of AVT. Radioimmunoassay of neonatal pituitary extracts (240–280 days) did not conclusively show AVT to be present, as the material assayed did not show parallelism with dilution. However, combined HPLC and radioimmunoassay of pooled extracts at this gestational age did demonstrate the presence of an immunoreactive AVT peak. Radioimmunoassay analysis of this peak indicated that a relatively small amount of AVT (at least 0·5 ng/gland) was present in the human pituitary gland at term.
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- 1983
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204. Response by Patel et al to Letter Regarding Article, "Radiation Induced DNA Damage in Operators Performing Endovascular Aortic Repair".
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Patel, Ashish S., El-Sayed, Tamer, Cho, Jun S., Kelly, James A., Ludwinski, Francesca E., Saha, Prakash, Lyons, Oliver T., Smith, Alberto, and Modarai, Bijan
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- 2018
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205. Relevance of Thrombophilia Testing in Patients Undergoing Iliofemoral Venous Stenting for Post-Thrombotic Occlusion
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Tincknell, Laura, Gwozdz, Adam, Jackson, Nicholas, Silickas, Justinas, Smith, Alberto, Saha, Prakash, Breen, Karen, and Black, Stephen
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- 2019
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206. Investigating a Role for Platelets in Venous In-Stent Stenosis in Patients with Post-Thrombotic Syndrome
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Gwozdz, Adam, Black, Stephen, Morris, Rachael, Messiha, Sophie, Ikram, Mohammed, Bye, Alexander, Gibbins, Jonathan, Rand, Margaret, Patel, Ashish, Modarai, Bijan, Smith, Alberto, and Saha, Prakash
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- 2021
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207. Encapsulation of macrophages enhances their retention and angiogenic potential.
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Ludwinski, Francesca E., Patel, Ashish S., Damodaran, Gopinath, Cho, Jun, Furmston, Joanna, Xu, Qingbo, Jayasinghe, Suwan N., Smith, Alberto, and Modarai, Bijan
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MACROPHAGES ,NEOVASCULARIZATION ,STEM cell treatment ,ISCHEMIA treatment ,CLINICAL trials - Abstract
Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300 µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P = 0.0001), and that this was associated both enhanced angiogenesis (P = 0.02) and arteriogenesis (P = 0.03), and an overall improvement in limb perfusion (P = 0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia. Limb ischemia: Encapsulation enhances therapeutic promise of immune cells in mice Blood vessel-promoting immune cells stay longer in the body and help promote blood flow to the feet and toes of mice with critical limb ischemia when the therapeutic cells are packaged inside tiny bubbles of a biocompatible seaweed derivative called alginate. A team led by Bijan Modarai from King's College London, UK, developed a reliable method for placing artery-stimulating macrophage cells inside alginate capsules measuring 300 micrometres in diameter, about the thickness of a postcard. In culture, the alginate coating had no effect on the macrophage viability; and when injected into the muscles of mice with artery blockages to their hindlimbs, the encapsulated cells were retained longer and offered greater therapeutic benefit than uncoated cells. This encapsulation strategy may improve the efficacy of comparable cell-based therapies for humans with limb ischemia. [ABSTRACT FROM AUTHOR]
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- 2019
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208. Abstract 14134: Fractional Flow Reserve is Better Than Duplex Ultrasound and Angiography for Predicting the Clinical Significance of Peripheral Arterial Lesions.
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Albayati, Mostafa A, Patel, Ashish, Hardy, Benjamin, Donati, Tommaso, Patel, Sanjay, Biasi, Lukla, Zayed, Hany, Monzon, Leo, Thulasidasan, Narayanan, Diamantopoulos, Athanasios, Perera, Divaka, Smith, Alberto, and Modarai, Bijan
- Published
- 2018
209. DIFFERENTIAL GENE EXPRESSION IN AREAS OF INSTABILITY IN CAROTID ARTERY PLAQUES
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Papaspyridonos, Marianna, Smith, Alberto, Cox, Joanne, Woollard, Rebecca, Roberts, Tracy, Burnand, Kevin, Suckling, Keith, and Patel, Lisa
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- 2004
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210. Tropoelastin
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Phinikaridou, Alkystis, Lacerda, Sara, Lavin, Begoña, Andia, Marcelo E., Smith, Alberto, Saha, Prakash, and Botnar, René M.
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211. Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation
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Lavin, Begoña, Lacerda, Sara, Andia, Marcelo, Lorrio, Silvia, Bakewell, Robert, Smith, Alberto, Rashid, Imran, Botnar, René, Phinikaridou, Alkystis, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université Francois Rabelais [Tours], King‘s College London, and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Dissections ,Matrix turnover ,Tropoelastin ,[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging ,[SDV]Life Sciences [q-bio] ,cardiovascular system ,Molecular imaging ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Aneurysm ,Elastin ,MRI - Abstract
International audience; Aims: Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulationof monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific magneticresonance contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlateswith aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed.....................................................................................................................................................................................................Methods and results:We utilized the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilationand performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement(LGE) magnetic resonance imaging (MRI) and T1 mapping at 3 T, with subsequent ex vivo validation. In across-sectional study (n = 66; control = 11, infused = 55) we found that Gd-TESMA enhanced MRI was elevated andconfined to dilated aortic segments (control: LGE=0.13 ± 0.04mm2, control R1= 1.1 ± 0.05 s-1 vs. dilated LGE=1.0 ± 0.4mm2, dilated R1 =2.4 ± 0.9 s-1) and was greater in segments with medium (8.0 ± 3.8mm3) and large(10.4 ± 4.1mm3) compared to small (3.6 ± 2.1mm3) vessel volume. Furthermore, a proof-of-principle longitudinalstudy (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expressionin dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment withpravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87 ± 0.3mm2 vs. 1.0 ± 0.44mm2) or aorticdilation (4.86 ± 2.44mm3 vs. 4.0 ± 3.6mm3). Importantly, Gd-TESMA-enhanced MRI identified accumulation of tropoelastinin excised human aneurysmal tissue (n = 4), which was confirmed histologically.....................................................................................................................................................................................................Conclusion: Tropoelastin MRI identifies dysfunctional matrix remodelling that is specifically expressed in regions of aortic aneurysmor dissection and correlates with the development and rate of aortic expansion. Thus, it may provide an additiveimaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with establishedaortopathy.
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212. Demonstration of immunoreactive arginine-vasotocin in human neonatal pituitaries
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SMITH, ALBERTO, primary and McINTOSH, NEIL, additional
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- 1985
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213. Plasma Arginine Vasopress in measured serially in the preterm newborn
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Mcintosh, Neil, primary and Smith, Alberto, additional
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- 1984
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214. Localized expression of carbonic anhydrase genes in liver and muscle detected by hybridization in situ
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KELLY, CHRISTIANE, primary, JEFFERY, STEPHEN, additional, SMITH, ALBERTO, additional, DE BOER, PIET, additional, MOORMAN, ANTOON, additional, and CARTER, NICK, additional
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- 1989
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215. The ontogeny of pituitary [arginine]vasopressin and oxytocin in the human foetus
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SMITH, ALBERTO, primary, McINTOSH, NEIL, additional, and CARTER, NICHOLAS, additional
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- 1982
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216. Tropoelastin: A Novel Marker for Plaque Progression and Instability.
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Phinikaridou, Alkystis, Lacerda, Sara, Lavin, Begoña, Andia, Marcelo E., Smith, Alberto, Saha, Prakash, and Botnar, René M.
- Abstract
Supplemental Digital Content is available in the text. Background: Elastolysis and ineffective elastogenesis favor the accumulation of tropoelastin, rather than cross-linked elastin, in atherosclerotic plaques. We developed gadolinium-labeled tropoelastin-specific magnetic resonance contrast agents for tropoelastin imaging in animal models. Methods and Results: Two peptides, VVGSPSAQDEASPLS and YPDHVQYTHY, were selected to target tropoelastin. In vitro binding, relaxivity, and biodistribution experiments enabled characterization of the probes and selecting the best candidate for in vivo magnetic resonance imaging. Magnetic resonance imaging was performed in atherosclerotic apolipoprotein E–deficient mice and New Zealand white rabbits with stable and rupture-prone plaques using a gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent. In addition, human carotid endarterectomy specimens were imaged ex vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and cross-linked elastin (64%±7% versus 1%±2%; P =0.001), had high in vitro relaxivity in solution (r
1-free =11.7±0.6 [mmol/L]−1 s−1 , r1-bound to tropoelastin =44±1 [mmol/L]− 1 s− 1 ), and favorable pharmacokinetics. In vivo mice vascular enhancement (4 weeks=0.13±0.007 mm2 , 8 weeks=0.22±0.01 mm2 , 12 weeks=0.33±0.01 mm2 ; P <0.001) and R1 relaxation rate (4 weeks=[0.90±0.01]/s, 8 weeks=[1.40±0.03]/s, 12 weeks=[1.87±0.04]/s; P <0.001) increased with atherosclerosis progression after gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent injection. Conversely, statin-treated (0.13±0.01 mm2 ; R1 =[1.37±0.03]/s) and control (0.10±0.005 mm2 ; R1 =[0.87±0.05]/s) mice showed less enhancement. Rupture-prone rabbit plaques had higher R1 relaxation rate compared with stale plaques (R1 =[2.26±0.1]/s versus R1 =[1.43±0.02]/s; P =0.001) after administration of the gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent that allowed detection of rupture-prone plaques with high sensitivity (84.4%) and specificity (92.3%). Increased vascular R1 relaxation rate was observed in carotid endarterectomy plaques after soaking (R1pre =[1.1±0.26]/s versus R1post =[3.0±0.1]/s; P =0.01). Ex vivo analyses confirmed the magnetic resonance imaging findings and showed uptake of the contrast agent to be specific for tropoelastin. Conclusions: Magnetic resonance imaging of tropoelastin provides a novel biomarker for atherosclerotic plaque progression and instability. [ABSTRACT FROM AUTHOR]- Published
- 2018
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217. Association of Concomitant Disease in the Profunda and Femoro-Popliteal Veins to Cumulative Patency and Re-Intervention Rates Following Ilio-Femoral Venous Stenting of Limbs with Postthrombotic Occlusion
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Fiengo, Leslie, Gwozdz, Adam, Saha, Prakash, Stephenson, Lawrence, Jones, Leonardo, Jackson, Nicholas, Silickas, Justinas, Kahn, Taha, Padayachee, Soundrie, Smith, Alberto, and Black, Stephen
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- 2019
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218. Redox dysregulation in the pathogenesis of chronic venous ulceration.
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Lyons, Oliver TA., Saha, Prakash, and Smith, Alberto
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PATHOLOGY , *WOUND healing , *OXIDATION-reduction reaction , *REACTIVE oxygen species , *FRACTURE healing , *HEALING ,LEG ulcers - Abstract
In chronic venous ulcers (CVUs), which account for up to 75% of leg ulcers, the inflammatory stage of wound healing fails to down-regulate, preventing progression to proliferation, remodeling and eventual epithelialisation. The roles of reactive oxygen species (ROS) in the oxidative burst and pathogen killing are well known, but ROS also have important functions in extra-cellular and intra-cellular signalling. Iron deposition, resulting from venous reflux, primes macrophages towards a persistent inflammatory response, with ongoing stimulation by bacteria potentially playing a role. Generation of excessive ROS by activated inflammatory cells causes tissue destruction and disintegration of the dermis, and then at later stages, a failure to heal. Here, we review the evidence for ROS in CVU formation and in normal and delayed healing. We also discuss how ROS modulation might be used to influence the healing of these complex wounds, which cause long-term morbidity and are associated with a significant financial burden to healthcare systems. • Chronic venous ulcers account for up to 75% of all leg ulcers. • Pathophysiology poorly understood but influenced by inflammat ion. • Tissue destruction and poor healing caused by excessive ROS generated by activated inflammatory cells. • Modulation of excessive ROS generation may promote chronic venous ulcer healing. [ABSTRACT FROM AUTHOR]
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- 2020
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219. Biological effects of radiation exposure during endovascular aortic aneurysm repair
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El-Sayed, Tamer, Modarai, Bijan, Patel, Ashish Satish, and Smith, Alberto
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Health risks associated with ionising radiation is a growing concern. Fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is associated with radiation exposure, particularly thoracoabdominal repairs using branched and/or fenestrated stent grafts. Conventional methods of measuring radiation exposure such as personal dosimeters or dose area product (DAP) do not give a true reflection of the biological effect of radiation exposure. In contrast, bio-dosimetry directly measures the effects of radiation exposure in biological specimens such as circulating lymphocytes, which are sensitive to radiation exposure and exhibit upregulation of DNA damage biomarkers such as γ-H2AX when exposed to ionising radiation (Beels, et. al., 2009) This study aimed to measure DNA damage/repair biomarkers in patients and operators after radiation exposure associated with EVAR. The expression of DNA damage/repair markers, γ-H2AX and phosphorylated ataxia telangiectasia mutated (pATM), was quantified in circulating lymphocytes in patients and operators during the peri-operative period of endovascular repair and compared with open aortic repair using flow cytometry. The role of leg shielding in radiation protection was assessed separately measuring these markers in the same operators wearing leg lead shielding and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators' blood in vitro. γ-H2AX and pATM levels increased significantly in patients and operators immediately after EVAR and recovered after 24 hrs. There was no change in γ-H2AX or pATM expression after open repair. Leg protection abrogated γ-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of γ-H2AX varied significantly when operators' blood was exposed to the same radiation dose in vitro. This is the first study to measure the acute DNA damage response in patients and operators after fluoroscopically guided aortic procedures and highlights the protective effect of leg shielding. Defining the relationship between this response and cancer risk may better inform safe levels of chronic low-dose radiation exposure and help to tailor individualised radiation protection strategies.
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- 2022
220. 3T BOLD MRI with low intrascan variability and high reproducibility of limb oxygenation measurements.
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Hedstrom, Erik, Patel, Ashish S., Voigt, Tobias, Modarai, Bijan, Schaeffter, Tobias, Smith, Alberto, and Nagel, Eike
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HYPERBARIC oxygenation - Abstract
An abstract of the conference paper "3T BOLD MRI with low intrascan variability and high reproducibility of limb oxygenation measurements," by Kelvin Chow and colleagues is presented.
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- 2012
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221. The role of alpha CGRP in L-NAME-induced hypertension
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Argunhan, Fulye, Brain, Susan Diana, and Smith, Alberto
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612.1 - Abstract
Calcitonin gene-related peptide (CGRP) is primarily localised and released from sensory nerves. It is a potent vasodilator neuropeptide with cardioprotective effects. The most common cardiovascular-relevant form is αCGRP. It signals via the CGRP receptor which is composed of the G-protein linked calcitonin like receptor (CLR) and an associated receptor associated modified protein (RAMP1); both of which are essential for function. There remains an unmet need in the treatment of cardiovascular disease and we hypothesised that CGRP acts via the CGRP receptor in an endothelial-independent manner to mediate its vasodilator and protective effects in vivo. The aim was to investigate the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME)-induced hypertension model in adult C57BL/6 wild-type (WT) and global αCGRP knock-out (KO) mice, which have similar baseline haemodynamics. The results showed that: i) αCGRP KO mice develop exacerbated hypertension in the presence of L-NAME, compared with WT mice and this was associated with adverse cardiovascular remodelling. This indicates that CGRP acts, at least in part, independently of endothelial-derived nitric oxide. ii) use of BIBN 4096 BS, a selective CGRP receptor antagonist supported these results, demonstrating the essential role of the CGRP receptor. No evidence was found for the involvement of a second proposed CGRP receptor (CTR/RAMP1). iii) RAMP1, but not CLR protein, from the CGRP receptor complex, was upregulated with L-NAME treatment. iv) αCGRP infusion reversed L-NAME-induced hypertension in αCGRP KO mice to the normotensive range. v) studies into the vascular site of CGRP’s protective action indicated that the mesenteric vessels, rather than the skin, play an important role in regulating the protective effect of CGRP; specifically, in first order mesenteric arterioles. This study in mice reveals that the therapeutic benefits of αCGRP extends to situations where endothelial dysfunction associated with reduced nitric oxide production exists.
- Published
- 2020
222. An increased frequency of the 5A allele in the promoter region of the MMP3 gene is associated with abdominal aortic aneurysms.
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Deguara, Jean, Burnand, Kevin G., Berg, Jonathan, Green, Peter, Lewis, Cathryn M., Chinien, Ganesh, Waltham, Matthew, Taylor, Peter, Stern, Rowena F., Solomon, Ellen, and Smith, Alberto
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- 2009
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223. A novel perfusion imaging strategy for the ischaemic limb
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Bajwa, Adnan Ahmad, Modarai, Bijan, and Smith, Alberto
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Current assessment of peripheral arterial disease (PAD) is focused on delineating luminal narrowing or obstruction in the major lower limb blood vessels. The imaging modalities used do not provide information on the microcirculation or muscle perfusion in the affected limb, the most important determinants of limb salvage in patients with PAD. An objective, non-invasive method for measuring and mapping muscle perfusion would aid diagnosis in PAD. It would may also inform planning of revascularisation strategies and better determine success after revascularization, ultimately improving limb salvage. Blood Oxygenation Level Dependent Magnetic Resonance Imaging (BOLD-MRI) is a technique that has been used to measure perfusion in the brain, kidneys and heart. The utility of BOLD-MRI in the lower limb musculature has, to date, been limited by a lack of sensitivity and reproducibility. The present study aimed to develop BOLD-MRI as an objective and reproducible tool for measuring perfusion in the calf musculature. The calf was imaged at 3 Tesla in young healthy controls, age-matched controls, and patients with critical limb ischaemia (CLI). A cuff placed around the thigh was used during the scan to provoke hyperaemia. T2* Signal intensity time curves were generated for each muscle group and curve parameters, including signal reduction during ischemia (SRi) and gradient during reactive hyperaemia (Grad). BOLD-MRI was also used to assess changes in perfusion following revascularization in CLI patients. Muscle biopsies, obtained at the level of BOLD-MRI measurement and from healthy proximal muscle of patients undergoing lower limb amputation were analysed for capillary:fibre (C:F) ratio. Good interuser and interscan reproducibility was found for Grad and SRi. The ischaemic limb had lower Grad and SRi compared with the contralateral asymptomatic limb, age-matched controls, and young controls. Successful revascularisation consistently resulted in significant improvement in both Grad and SRi. There was a significant correlation between C:F ratio in muscle biopsies from amputated limbs and Grad measured preoperatively at the corresponding level. These data suggest that BOLD-MRI holds promise as a reliable tool for assessing perfusion in the lower limb and may allow refinement of current treatment algorithms. Its utility merits further investigation in a multi-centre clinical trial.
- Published
- 2018
224. Venous Thrombosis Accelerates Atherosclerosis in Mice.
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Saha, Prakash, Gutmann, Clemens, Kingdon, Jack, Dregan, Alexandru, Bertolaccini, Laura, Grover, Steven P., Patel, Ashish S., Modarai, Bijan, Lyons, Oliver, Schulz, Christian, Andia, Marcelo E., Phinikaridou, Alkystis, Botnar, René M., and Smith, Alberto
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VENOUS thrombosis , *ATHEROSCLEROTIC plaque , *MACROPHAGE inflammatory proteins , *CAROTID intima-media thickness , *MICE , *TUMOR necrosis factors , *ATHEROSCLEROSIS - Abstract
Assessments of venous thrombi and atherosclerosis were performed in vivo using magnetic resonance imaging of the inferior vena cava and of the brachiocephalic artery (BCA).[2],[3] Next, we assessed whether removal of DVT would affect the plaque. Keywords: atherosclerosis; inflammation; magnetic resonance imaging; molecular imaging; monocytes; thromboinflammation; venous thrombosis EN atherosclerosis inflammation magnetic resonance imaging molecular imaging monocytes thromboinflammation venous thrombosis 1945 1947 3 06/16/23 20230620 NES 230620 Deep vein thrombosis (DVT) and atherosclerosis cause significant morbidity and can lead to death. Here, we hypothesized that an increase in arterial events after venous thrombosis occurs because DVT directly accelerates atherosclerosis through a process involving DVT-induced inflammation. [Extracted from the article]
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- 2023
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225. THE BLOOD PRESSURE (BP) RESPONSE TO THERMAL INJURY IN CHILDHOOD.293
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McIntosh, Neil, Barclay, Cameron, Sedowofia, Kofi, Smith, Alberto, Stephen, Rhona, and Thomson, Margaret
- Published
- 1996
226. An investigation of Tie2 expressing monocytes/macrophages in the context of limb ischaemia
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Furmston, Joanna, Modarai, Bijan, and Smith, Alberto
- Abstract
Therapeutic neovascularisation has the potential to salvage ischaemic limbs that are not amenable to conventional treatments. Results of clinical trials have been disappointing however, likely due to the failure to deliver potent angiogenic cells in sufficient numbers, and poor retention of cells in the target tissue. Monocytes (CD14+ cells) expressing the angiopoietin receptor, tyrosine kinase with immunoglobulin and EGF homology domains (TIE2), are highly angiogenic and regulate revascularisation of the ischaemic limb, but are only present in low numbers in the circulation. Tamm-Horsfall protein 1 (THP1) cells and immortalised bone marrow derived macrophages (iBMM cells) were transduced with a Tie2 expressing lentivirus. Intact Tie2 receptor signalling was confirmed using Phosflow. Expression of angiogenic genes was investigated after angiopoietin 1 (Ang1) or angiopoietin 2 (Ang2) stimulation, using quantitative polymerase chain reaction (qPCR). Transduced THP1 cells and iBMM cells (1x106 per mouse) were injected into the ischaemic hind limb and limb perfusion was analysed using laser Doppler. Cells were encapsulated in alginate and the effect on their phenotype, viability and angiogenic potential was investigated. Ang1 stimulation promoted phosphorylation of the Tie2 receptor in Tie2 transduced THP1 and iBMM cells and significantly up-regulated the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and monocyte chemoattractant protein 1 (MCP1) (P<0.05 for all). Tie2 transduced THP1 cells and iBMM cells accelerated reperfusion of the ischaemic hindlimb at day 7 and 14 when compared with controls (P<0.001). Arteriole diameter was significantly higher in hindlimb muscle treated with Tie2 expressing iBMM cells. Encapsulated iBMMs remained viable and retained their phenotype for 7 days, but had an attenuated angiogenic potential compared with their naked counterparts. Forcing the expression of Tie2 in immortalised monocytes/macrophages confers potent angiogenic properties. Transducing a general population of primary human monocytes with the Tie2 lentivirus used, may represent a strategy for generating large numbers of Tie2 expressing monocytes/macrophages (TEMs) for clinical use. The utility of encapsulation to enhance cell retention remains uncertain as our preliminary results suggest that encapsulation impairs angiogenic activity in TEMs.
- Published
- 2016
227. Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice.
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Bazigou, Eleni, Lyons, Oliver T. A., Smith, Alberto, Venn, Graham E., Cope, Celia, Brown, Nigel A., and Makinen, Taija
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VENOUS valves , *VEIN diseases , *GENES , *MORPHOGENESIS , *HYPERTENSION , *LABORATORY mice , *LYMPH circulation , *GENETICS , *ENDOTHELIUM physiology , *VEIN physiology , *ANIMAL experimentation , *BIOLOGICAL models , *CELL receptors , *COMPARATIVE studies , *EPITHELIAL cells , *FIBRONECTINS , *RESEARCH methodology , *MEDICAL cooperation , *MEMBRANE proteins , *MICE , *RESEARCH , *RESEARCH funding , *PHENOTYPES , *EVALUATION research , *FETAL development - Abstract
Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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228. Role of functional imaging in determining inflammation and extracellular matrix degradation in aortic aneurysms
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Attia, Rizwan, Smith, Alberto, Waltham, Matthew, and Modarai, Bijan
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616.1 - Abstract
Aneurysmal disease of the aorta is a degenerative condition characterised by inflammation and extracellular protein loss, in particular, loss of cross-linked elastin. 18F-FDG is currently the most widely available tracer used in assessing the metabolic activity of tissues and is known to be taken up in aneurysmal wall, but its biological correlates, other than metabolism, have yet to be evaluated. Other novel tracers for more specific functional imaging of proteins such as elastin in the aneurysm wall have also yet to be evaluated in the context of aneurysmal disease. 18F-FDG uptake in aneurysms was characterised using a combination of laser scintigraphic 3D aortic masks generated from PET-CT that allowed precise aortic biopsy of areas of high and low tracer uptake. Positive correlations were obtained between 18F-FDG uptake and total leukocyte, B-cell, T-cell and NK-cell content in human aneurysmal wall, while elastin and collagen content was reduced at sites of inflammatory cell infiltrate. B and T-cells had significant modulatory affects on vascular smooth muscle cell (VSMC) proliferation, survival and protein synthesis in-vitro. 18F-FDG uptake and its inflammatory correlates were similarly characterised in ApoE-/--ATII model. There was a temporal, heterogeneous 18F-FDG uptake in the aneurysms associated with increased immune cell content, but no correlation was found between uptake and aortic expansion or diameter. Elastin-specific MR contrast agent (ESMA) uptake was characterised in the ApoE-/--ATII model and found to correlate with elastin, tropoelastin, immune cell content and extracellular matrix organisation, as well as aortic expansion. Treatment with elastin modulating antagomirs decreased aneurysm expansion and rupture. This was through modulated down-stream gene and protein expression of proteins and enzymes involved in elastin and collagen homeostasis namely TGFβ, LOX and MMP’s. It appears therefore that 18F-FDG uptake correlates with specific immune cell infiltrates, in particular that of B- and T-cells that can modulate VSMC function. There are distinct cellular populations that are responsible for a pro-aneurysmal phenotype and B-T-regulatory cell populations that lead to aortic remodeling response. ESMA uptake was related to elastin remodelling and may provide a novel predictor of aneurysm behavior. Antagomir mediated alteration of VSMC phenotype might alter the natural history of aneurysmal disease.
- Published
- 2015
229. Multimodality imaging of the abdominal aortic aneurysm
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Abbas, Abeera, Waltham, Matthew, Smith, Alberto, and Modarai, Bijan
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616.1 - Abstract
Age and hypertension lead to aortic remodeling and stiffness and are also major risk factors for abdominal aortic aneurysms (AAA). This study aimed to investigate: (i) the use of multimodal imaging to test the hypothesis that aneurysmal disease of the abdominal aorta is a remodeling response to aortic stiffness and systolic hypertension; (ii) the utility of a novel ultrasound-based device (AortaScan) for detection of AAA in the community setting. We used multimodality imaging tonometry and cardiovascular magnetic resonance imaging (CMR) to quantify pulse wave velocity (PWV, a measure of stiffness), in the aortic arch (Arch), thoracic aorta (TA) and the abdominal aorta (AA). Stiffness was also correlated with measures of calcification and metabolic activity measured on CT and PET/CT respectively. The thoracic aortae of patients with AAA were stiffer than those of sex matched controls. Although systolic hypertension was more common in AAA patients, multivariate analysis revealed that aortic stiffness and mean arterial pressure were associated with AAA disease. The likelihood of developing AAA disease increases >3-fold for 1m/sec increase in PWV. This data suggests that segmental stiffness is modified in the presence of AAA and provides further evidence that aneurysm formation may be an adaptive remodeling response to hypertension. The AortaScan can detect AAA without the need for a trained operator and has potential in a community-based screening programme. It would, however, need further technical improvement to increase sensitivity before it could be considered a replacement for trained screening personnel.
- Published
- 2015
230. Prolyl hydroxylase domain proteins in venous thrombus resolution
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Grover, Steven Philip, Modarai, Bijan, and Smith, Alberto
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617.4 - Abstract
The prolyl hydroxylase domain (PHD) proteins serve as critical regulators of the cellular response to tissue hypoxia, like that present in the early venous thrombus, through regulation of hypoxia-inducible factor 1α (HIF1α) stability. This study sought to determine: (i) the expression of PHD1, PHD2 and PHD3 at the gene and protein level during natural thrombus resolution; (ii) the effect of gene specific deletion of Phd2 on thrombus resolution; (iii) the effect of pan- PHD inhibition on thrombus resolution; and (iv) the contribution of endogenous VEGFR signalling to thrombus resolution. All three PHD isoforms were expressed in the naturally resolving thrombus at the gene and protein level. Gene expression of Phd1 remained invariant while Phd2 and Phd3 expression demonstrated distinct temporal patterns. PHD isoforms were localised to the cellular component of the thrombus, with morphological analysis suggesting expression in both neutrophils and macrophages. Constitutive heterozygous Phd2 gene deletion failed to increase HIF1α stabilisation as was not associated with increased thrombus resolution. Inducible homozygous Phd2 gene deletion significantly enhanced HIF1α nuclear accumulation and transcriptional activity but thrombus resolution was unchanged. Pharmacological inhibition of PHD isoforms with novel small molecule inhibitor, AKB-4924 and JNJ-42041935, signficantly increased HIF1α nuclear accumulation and transcriptional activity. Treatment with these inhibitors significantly increased thrombus neovascularisation but thrombus resolution was unaffected. Blocking of endogenous VEGFR signalling using the pan- VEGFR inhibitor axitinib significantly impaired thrombus resolution. Axitinib treated thrombi remained larger and more occlusive for an extended period of time and this was associated with significant reductions in thrombus neovascularisation, macrophage recruitment and collagen deposition. Inhibition of PHD activity promotes thrombus neovascularisation, but other mechanisms are likely to regulate the removal of thrombus. Studies of thrombus resolution in Phd2 gene specific knockouts indicate that PHD2 activity does not play a major role in thrombus resolution. However, endogenous VEGFR signalling activity, downstream of HIF, is necessary for thrombus resolution.
- Published
- 2015
231. Regulation of venous valve development and maintenance
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Lyons, Oliver Timothy and Smith, Alberto
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616.1 - Abstract
Venous valve failure and associated venous hypertension is common in man, yet very little is known about the development and maintenance of venous valves. Existing therapies for valve failure most commonly involve removal or ablation of the vein in the superficial venous system. Little can be done to correct reflux in the deep veins. Immunofluorescence and electron microscopy were used to visualise and quantify venous valves at different stages of development in an experimental mouse model. Several proteins previously thought to be specific markers for arterial or lymphatic endothelium were found in venous endothelia and venous valves. Constitutive and conditional loss of function genetic approaches revealed how an initially homogenous population of endothelial cells acquire distinct expression patterns and behaviours, but act co-ordinately to orchestrate valve formation. The expression of several factors, previously found to be required for cardiac and/or lymphatic valve formation, was also found to be important for venous valve formation, including connexins 37, 43 and 47, integrin-α9, ephrinB2, Foxc2, and NFAT-calcineurin. Mutations in VEGFR3, FOXC2, GJC2 and GJA1 were found to be associated with structural venous valve defects in man. It has been postulated that fluid flows regulate lymphatic and venous valve development in vivo. A novel model of altered blood flow was developed, and used to show that normal blood flow is required for postnatal valve development. These data enhance our understanding of the cellular mechanisms underlying human venous valve disease caused by mutations in VEGFR3, FOXC2, GJC2 and GJA1, and suggest novel candidate genes, such as Itga9 and GJA4 for human venous valve disease. Improved knowledge of the factors regulating venous valves could lead to new treatments for valve failure, or regenerative medicine approaches to venous reflux.
- Published
- 2015
232. Higher Incidence of Chromosomal Aberrations in Operators Performing a Large Volume of Endovascular Procedures.
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Abdelhalim, Mohamed A., Patel, Ashish, Moquet, Jayne, Saha, Prakash, Smith, Alberto, Badie, Christophe, Anderson, Rhona, Ainsbury, Elizabeth, and Modarai, Bijan
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CHROMOSOME abnormalities , *ENDOVASCULAR surgery , *RADIATION dosimetry , *IN situ hybridization , *DISEASE incidence , *RESEARCH funding - Abstract
In this aberration, breaks in 2 chromosomes followed by an incorrect repair have resulted in the formation of a single chromosome containing 2 centromeres and a chromosome fragment containing no centromeres. The centromere-containing portion of chromosome 10 has attached to chromosome 8, and the acentric portion has attached to chromosome 1. [Extracted from the article]
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- 2022
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233. X-box binding protein 1-mediated COL4A1s secretion regulates communication between vascular smooth muscle and stem/progenitor cells.
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Angbohang, Angshumonik, Lei Huang, Yi Li, Yue Zhao, Yijie Gong, Yi Fu, Chenfeng Mao, Morales, Jose, Peiyi Luo, Ehteramyan, Mazdak, Yingtang Gao, Margariti, Andriana, Wenduo Gu, Min Zhang, Smith, Alberto, Shah, Ajay M., Tong Li, Wei Kong, and Lingfang Zeng
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CARRIER proteins , *VASCULAR smooth muscle , *PROGENITOR cells , *WESTERN immunoblotting , *PHENOTYPIC plasticity , *CARCINOEMBRYONIC antigen , *COLLAGEN - Abstract
Vascular smooth muscle cells (VSMCs) contribute to the deposition of extracellular matrix proteins (ECMs), including Type IV collagen, in the vessel wall. ECMs coordinate communication among different cell types, but mechanisms underlying this communication remain unclear. Our previous studies have demonstrated that X-box binding protein 1 (XBP1) is activated and contributes to VSMC phenotypic transition in response to vascular injury. In this study, we investigated the participation of XBP1 in the communication between VSMCs and vascular progenitor cells (VPCs). Immunofluorescence and immunohistology staining revealed that Xbp1 gene was essential for type IV collagen alpha 1 (COL4A1) expression during mouse embryonic development and vessel wall ECM deposition and stem cell antigen 1-positive (Sca1+)-VPC recruitment in response to vascular injury. The Western blot analysis elucidated an Xbp1 gene dose-dependent effect on COL4A1 expression and that the spliced XBP1 protein (XBP1s) increased protease-mediated COL4A1 degradation as revealed by Zymography. RT-PCR analysis revealed that XBP1s in VSMCs not only upregulated COL4A1/2 transcription but also induced the occurrence of a novel transcript variant, soluble type IV collagen alpha 1 (COL4A1s), in which the front part of exon 4 is joined with the rear part of exon 42. Chromatinimmunoprecipitation, DNA/protein pulldown and in vitro transcription demonstrated that XBP1s binds to exon 4 and exon 42, directing the transcription from exon 4 to exon 42. This leads to transcription complex bypassing the internal sequences, producing a shortened COL4A1s protein that increased Sca1+-VPC migration. Taken together, these results suggest that activated VSMCs may recruit Sca1+-VPCs via XBP1s-mediated COL4A1s secretion, leading to vascular injury repair or neointima formation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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234. Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair.
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El-Sayed, Tamer, Patel, Ashish S., Cho, Jun S., Kelly, James A., Ludwinski, Francesca E., Saha, Prakash, Lyons, Oliver T., Smith, Alberto, Modarai, Bijan, and Guy’s and St Thomas’ Cardiovascular Research Collaborative
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PHYSIOLOGICAL effects of radiation , *DNA damage , *RADIOBIOLOGY , *ENDOVASCULAR surgery , *BIOCHEMICAL genetics , *THERAPEUTICS , *HEALTH , *PROTEIN metabolism , *ABDOMINAL aortic aneurysms , *DNA , *FLUOROSCOPY , *IMMUNOHISTOCHEMISTRY , *LEG , *PHOSPHORYLATION , *PROTEIN kinases , *RADIATION , *RESEARCH funding , *T cells , *OCCUPATIONAL hazards , *ENVIRONMENTAL exposure , *EQUIPMENT & supplies - Abstract
Background: Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR.Methods: Expression of the DNA damage/repair marker, γ-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators' blood in vitro.Results: γ-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (P<0.0003 for both). Only pATM levels increased after infrarenal endovascular aortic repair (P<0.04). Expression of both markers fell to baseline in operators after 24 hours (P<0.003 for both). There was no change in γ-H2AX or pATM expression after open repair. Leg protection abrogated γ-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of γ-H2AX varied significantly when operators' blood was exposed to the same radiation dose in vitro (P<0.0001).Conclusions: This is the first study to detect an acute DNA damage response in operators performing fluoroscopically guided aortic procedures and highlights the protective effect of leg shielding. Defining the relationship between this response and cancer risk may better inform safe levels of chronic low-dose radiation exposure. [ABSTRACT FROM AUTHOR]- Published
- 2017
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235. Quantification of experimental venous thrombus resolution by longitudinal nanogold-enhanced micro-computed tomography.
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Grover, Steven P., Saha, Prakash, Jenkins, Julia, Mukkavilli, Arun, Lyons, Oliver T., Patel, Ashish S., Sunassee, Kavitha, Modarai, Bijan, and Smith, Alberto
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VENOUS thrombosis , *THROMBOSIS prevention , *GOLD nanoparticles , *COMPUTED tomography , *CONTRAST-enhanced ultrasound , *IMAGE reconstruction - Abstract
Introduction The assessment of thrombus size following treatments directed at preventing thrombosis or enhancing its resolution has generally relied on physical or histological methods. This cross-sectional design imposes the need for increased numbers of animals for experiments. Micro-computed tomography (microCT) has been used to detect the presence of venous thrombus in experimental models but has yet to be used in a quantitative manner. In this study, we investigate the use of contrast-enhanced microCT for the longitudinal assessment of experimental venous thrombus resolution. Materials and methods Thrombi induced by stenosis of the inferior vena cava in mice were imaged by contrast-enhanced microCT at 1, 7 and 14 days post-induction (n = 18). Thrombus volumes were determined longitudinally by segmentation and 3D volume reconstruction of microCT scans and by standard end-point histological analysis at day 14. An additional group of thrombi were analysed solely by histology at 1, 7 and 14 days post-induction (n = 15). Results IVC resident thrombus was readily detectable by contrast-enhanced microCT. MicroCT-derived measurements of thrombus volume correlated well with time-matched histological analyses (ICC = 0.75, P < 0.01). Thrombus volumes measured by microCT were significantly greater than those derived from histological analysis (P < 0.001). Intra- and inter-observer analyses were highly correlated (ICC = 0.99 and 0.91 respectively, P < 0.0001). Further histological analysis revealed noticeable levels of contrast agent extravasation into the thrombus that was associated with the presence of neovascular channels, macrophages and intracellular iron deposits. Conclusion Contrast-enhanced microCT represents a reliable and reproducible method for the longitudinal assessment of venous thrombus resolution providing powerful paired data. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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236. Postsurgical Inflammation as a Causative Mechanism of Venous Thromboembolism.
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Albayati, Mostafa A., Grover, Steven P., Saha, Prakash, Lwaleed, Bashir A., Modarai, Bijan, and Smith, Alberto
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PULMONARY embolism , *THROMBOEMBOLISM risk factors , *SURGICAL complications , *NEUTROPHILS , *PATHOLOGICAL physiology , *DISEASE incidence , *THERAPEUTICS ,THROMBOEMBOLISM treatment - Abstract
Surgery is associated with an increased risk of venous thromboembolic events (VTE) including deep vein thrombosis and pulmonary embolism. Although the current treatment regiments such as mechanical manipulation and administration of pharmacological prophylaxis significantly reduced the incidence of postsurgical VTE, they remain a major cause of postoperative morbidity and mortality worldwide. The pathophysiology of venous thrombosis traditionally emphasizes the series of factors that constitute Virchow triad of factors. However, inflammation can also be a partof this by giving rise to a hypercoagulable state and endothelial damage. The inflammatory response after surgery, which is initiated by a cytokine "storm" and occurs within hours of surgery, creates a prothrombotic environment that is further accentuated by several cellular processes including neutrophil extracellular traps formation, platelet activation, and the generation of tissue factor-bearing microparticles. Although such inflammatory markers are elevated in undergoing surgery, the precise mechanism by which they give rise to venous thrombosis is poorly understood. Here, we discuss the potentialmechanisms linking inflammation to thrombosis, and highlight strategies that may minimize surgical inflammation and reduce the incidence of postoperative VTE. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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237. Suppression of angiogenic response in local vein wall is associated with reduced thrombus resolution.
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Evans, Colin E., Grover, Steven P., Saha, Prakash, Humphries, Julia, Jung-whan Kim, Modarai, Bijan, and Smith, Alberto
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IMMUNOSUPPRESSION , *VASCULAR endothelial growth factors , *ESTRADIOL , *NEOVASCULARIZATION , *LABORATORY mice , *CONTROL groups - Abstract
Introduction The formation of new vascular channels within and around venous thrombus contributes to its resolution. Neovascularisation arising from the surrounding vein may facilitate this process. Treatment of cancer patients with anti-angiogenic agents can lead to increased incidence of venous thromboembolic events, but the effect of these agents on the processes that govern thrombus resolution are unclear. The aim of this study was to determine the effect of anti-angiogenic treatment with 2-methoxyestradiol (2ME) on (i) angiogenic response in the thrombosed vein and (ii) venous thrombus resolution. Materials and methods Venous thrombus was induced in the inferior vena cava (IVC) of 36 adult male BALB/C mice. Thrombosed mice received either the anti-angiogenic agent, 2ME (150 mg/kg/day, i/p), or vehicle control (n = 18/group). In the thrombosed IVC of both groups: hypoxia-inducible factor (HIF) 1?, and its angiogenic targets, vascular endothelial growth factor (VEGF) and placental growth factor (PLGF), were quantified using enzyme-linked immunosorbent assays at days 1 and 10 post-thrombus induction (n = 6/group); and inflammatory cell content, cell proliferation, and vein recanalisation were quantified using immunostaining and image analysis at day 10 (n = 6/group). Results In the IVC of mice treated with 2ME compared with control: HIF1? (P < 0.005 and P < 0.02), VEGF (P < 0.005 and P < 0.02), and PLGF levels (P < 0.01 and P < 0.001) were reduced at days 1 and 10 post-thrombus induction respectively, and macrophage content (P < 0.005), neutrophil content (P < 0.01), vein recanalistion (P < 0.05), and thrombus resolution (P < 0.001) were also reduced at day 10. Conclusions Anti-angiogenic treatment with 2ME supressed the HIF1-mediated angiogenic drive in local vein wall and attenuated venous thrombus resolution. The potential pro-thrombotic effect of anti-angiogenic agents should be carefully considered when managing venous thromboembolic events in cancer patients. Abbreviations 2ME, 2-methoxyestradiol; HIF, hypoxia-inducible factor; IVC, inferior vena cava; PLGF, placental growth factor; VEGF, vascular endothelial growth factor [ABSTRACT FROM AUTHOR]
- Published
- 2014
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238. Upregulation of hypoxia-inducible factor 1 alpha in local vein wall is associated with enhanced venous thrombus resolution
- Author
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Evans, Colin E., Humphries, Julia, Waltham, Matthew, Saha, Prakash, Mattock, Katherine, Patel, Ashish, Ahmad, Anwar, Wadoodi, Ashar, Modarai, Bijan, Burnand, Kevin, and Smith, Alberto
- Subjects
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HYPOXEMIA , *THROMBOSIS , *VASCULAR endothelial growth factors , *GROWTH factors , *VENA cava inferior , *NEOVASCULARIZATION , *MIMOSINE , *TRANSCRIPTION factors - Abstract
Abstract: Introduction: Venous thrombus resolution may be regulated by an angiogenic process that involves the surrounding vein wall. The aims of this study were to determine whether: (i) thrombosis stimulates activation of the angiogenic transcription factor, hypoxia-inducible factor (HIF) 1α, and downstream expression of growth factors in vein wall; and (ii) upregulation of HIF1α in vein wall leads to increased growth factor expression and enhanced thrombus resolution. Materials and methods: HIF1α, vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) were quantified in mouse inferior vena cava (IVC) at days 1, 3, 7, and 14 after thrombus formation (n=10-13 per group). An additional group of thrombosed mice were treated with the prolyl-hydroxylase domain (PHD) inhibitor, L-mimosine (L-mim) or vehicle control. HIF1α, VEGF, and PLGF in IVC were measured at days 1 and 7; and vein recanalisation and thrombus resolution were measured at days 7 and 10 (n=6-7 per group). Results: HIF1α was expressed in thrombosed IVC and its levels remained relatively constant throughout natural resolution. The levels of VEGF in thrombosed IVC were elevated at days 1 (P<0.0001) and 3 (P<0.05); and PLGF at days 1 (P<0.0001), 3 (P<0.0001), and 7 (P<0.0001). Treatment with L-mim led to: increased HIF1α (P<0.05), VEGF (P<0.005), and PLGF (P<0.001) levels in the IVC; decreased thrombus size (P<0.01); and increased vein recanalisation (P<0.001). Conclusions: HIF1α levels in vein wall are not affected by thrombosis and it appears that the angiogenic drive in the vein surrounding resolving thrombus is regulated independently of HIF1α. Stimulating HIF1α levels in the vein wall leads to an increased angiogenic drive and promotes vein recanalisation and thrombus resolution. [Copyright &y& Elsevier]
- Published
- 2011
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239. Mutations in FOXC2 in Humans (Lymphoedema Distichiasis Syndrome) Cause Lymphatic Dysfunction on Dependency.
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Mellor, Russell H., Tate, Naomi, Stanton, Anthony W.B., Hubert, Charlotte, Mäkinen, Taija, Smith, Alberto, Burnand, Kevin G., Jeffery, Steve, Levick, J. Rodney, and Mortimer, Peter S.
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GENETIC mutation , *EDEMA , *IMMUNOHISTOCHEMISTRY , *LYMPHATIC abnormalities , *LABORATORY mice , *TRANSCRIPTION factors , *PHYSIOLOGY - Abstract
Background: Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function. Methods: We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin. Results: FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls. Conclusions:FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2011
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240. Assessment of atherosclerotic plaque burden with an elastin-specific magnetic resonance contrast agent.
- Author
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Makowski, Marcus R., Wiethoff, Andrea J., Blume, Ulrike, Cuello, Friederike, Warley, Alice, Jansen, Christian H. P., Nagel, Eike, Razavi, Reza, Onthank, David C., Cesati, Richard R., Marber, Michael S., Schaeffter, Tobias, Smith, Alberto, Robinson, Simon P., and Botnar, René M
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ATHEROSCLEROTIC plaque , *ELASTIN , *INTRAVASCULAR ultrasonography , *MAGNETIC resonance imaging , *DISEASE progression , *LABORATORY mice - Abstract
Atherosclerosis and its consequences remain the main cause of mortality in industrialized and developing nations. Plaque burden and progression have been shown to be independent predictors for future cardiac events by intravascular ultrasound. Routine prospective imaging is hampered by the invasive nature of intravascular ultrasound. A noninvasive technique would therefore be more suitable for screening of atherosclerosis in large populations. Here we introduce an elastin-specific magnetic resonance contrast agent (ESMA) for noninvasive quantification of plaque burden in a mouse model of atherosclerosis. The strong signal provided by ESMA allows for imaging with high spatial resolution, resulting in accurate assessment of plaque burden. Additionally, plaque characterization by quantifying intraplaque elastin content using signal intensity measurements is possible. Changes in elastin content and the high abundance of elastin during plaque development, in combination with the imaging properties of ESMA, provide potential for noninvasive assessment of plaque burden by molecular magnetic resonance imaging (MRI). [ABSTRACT FROM AUTHOR]
- Published
- 2011
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241. The monocyte/macrophage as a therapeutic target in atherosclerosis
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Saha, Prakash, Modarai, Bijan, Humphries, Julia, Mattock, Katherine, Waltham, Matthew, Burnand, Kevin G, and Smith, Alberto
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ATHEROSCLEROTIC plaque , *TARGETED drug delivery , *MONOCYTES , *MACROPHAGES , *BIOMARKERS , *OXIDATIVE stress , *BLOOD cholesterol , *INFLAMMATION , *THERAPEUTICS - Abstract
It is now clear that the monocyte/macrophage has a crucial role in the development of atherosclerosis. This cell appears to be involved in all stages of atherosclerotic plaque development and is increasingly seen as a candidate for therapeutic intervention and as a potential biomarker of disease progression and response to therapy. The main mechanisms related to the activity of the monocyte/macrophage that have been targeted for therapy are those that facilitate recruitment, cholesterol metabolism, inflammatory activity and oxidative stress. There is also increasing evidence that there is heterogeneity within the monocyte/macrophage population, which may have important implications for plaque development and regression. A better insight into how specific phenotypes may influence plaque progression should facilitate the development of novel methods of imaging and more refined treatments. [Copyright &y& Elsevier]
- Published
- 2009
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242. Electrospray Ionization Mass Spectrometry Identifies Substrates and Products of Lipoprotein-associated Phospholipase A2 in Oxidized Human Low Density Lipoprotein.
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Davis, Bill, Koster, Grielof, Douet, Lisa J., Scigelova, Michaela, Woffendin, Gary, Ward, Joanna M., Smith, Alberto, Humphries, Julia, Burnand, Kevin G., Macphee, Cohn H., and Postle, Anthony D.
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LOW density lipoproteins , *PHOSPHOLIPASES , *OXIDATION , *ATHEROSCLEROSIS , *PHOSPHATIDATE phosphatase , *LECITHIN , *ELECTROSPRAY ionization mass spectrometry - Abstract
There is increasing evidence that modified phospholipid products of low density lipoprotein (LDL) oxidation mediate inflammatory processes within vulnerable atherosclerotic lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is present in vulnerable plaque regions where it acts on phospholipid oxidation products to generate the pro-inflammatory lysophsopholipids and oxidized non-esterified fatty acids. This association together with identification of circulating Lp-PLA2 levels as an independent predictor of cardiovascular disease provides a rationale for development of Lp-PLA2 inhibitors as therapy for atherosclerosis. Here we report a systematic analysis of the effects of in vitro oxidation in the absence and presence of an Lp-PLA2 inhibitor on the phosphatidylcholine (PC) composition of human LDL. Mass spectrometry identifies three classes of PC whose concentration is significantly enhanced during LDL oxidation. Of these, a series of molecules, represented by peaks in the m/z range 594-666 and identified as truncated PC oxidation products by accurate mass measurements using an LTQ Orbitrap mass spectrometer, are the predominant substrates for Lp-PLA2. A second series of oxidation products, represented by peaks in the m/z range 746-830 and identified by LTQ Orbitrap analysis as non-truncated oxidized PCs, are quantitatively more abundant but are less efficient Lp-PLA2 substrates. The major PC products of Lp-PLA2, saturated and mono-unsaturated lyso-PC, constitute the third class. Mass spectrometric analysis confirms the presence of many of these PCs within human atherosclerotic lesions, suggesting that they could potentially be used as in vivo markers of atherosclerotic disease progression and response to Lp-PLA2 inhibitor therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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243. The effect of anticoagulation with subcutaneously delivered polyethylene glycol conjugated hirudin and recombinant tissue plasminogen activator on recurrent stenosis in the rabbit double-balloon injury model
- Author
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Alexander, Barry, Burnand, Kevin G., Lattimer, Christopher L., Humphries, Julia, Gaffney, Patrick J., Eastham, David, and Smith, Alberto
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HYPERPLASIA , *BLOOD coagulation , *POLYETHYLENE glycol , *PLASMINOGEN - Abstract
Myointimal hyperplasia is the condition usually responsible for recurrent stenosis (restenosis) after endarterectomy, bypass grafting and angioplasty. Its cause is still not known. The present study examined whether inhibition of thrombin by tissue plasminogen activator (r-TPA) or polyethylene glycol recombinant hirudin (PEG-hirudin) could reduce restenosis in an animal model. Restenosis was induced in 20 cholesterol-fed rabbits. The right carotid artery underwent a double-balloon injury while left carotid artery acted as a control. Recombinant tissue plasminogen activator (1 mg kg−1 s.c.) and PEG-hirudin (0.7 mg kg−1 s.c.) were given subcutaneously with normal saline acting as a control. Blood levels of PEG-hirudin were measured by both ELISA and an Ecarin (activity) assay. Vessel dimensions were measured in histological sections, obtained from perfusion-fixed tissue, using computerised planimetry. The model reproduced many of the histological changes found in human restenosis, such as intramural thrombus, rupture of the elastic lamina, macrophage infiltration and smooth muscle migration. Reinjury caused an almost three-fold reduction in the area of the lumen (median 0.25 mm2) compared with uninjured vessels (median 0.72 mm2). The mean plasma levels of PEG-hirudin and r-tPA achieved were 291 ng/ml (S.E.M. 28 ng/ml) and 34 IU/ml (S.E.M. 12 IU/ml), respectively. PEG-hirudin significantly inhibited the effect of balloon injury on luminal area compared with saline-treated controls (0.21 versus 0.44 mm2, respectively, P<0.05). Recombinant tPA also had a similar inhibitory affect, but this did not reach statistical significance (0.16 versus 0.44 mm2, respectively, P>0.05). The magnitude of luminal narrowing was significantly reduced by subcutaneous injection of PEG-hirudin. Further studies are required to determine whether this effect can be enhanced by other antithrombins or improved methods of delivery. [Copyright &y& Elsevier]
- Published
- 2004
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244. A subpopulation of tissue remodeling monocytes stimulates revascularization of the ischemic limb.
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Patel AS, Ludwinski FE, Kerr A, Farkas S, Kapoor P, Bertolaccini L, Fernandes R, Jones PR, McLornan D, Livieratos L, Saha P, Smith A, and Modarai B
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- Humans, Animals, Receptors, IgG metabolism, Mice, Male, Vascular Endothelial Growth Factor A metabolism, Female, Aged, Middle Aged, Cell Movement, Heparin-binding EGF-like Growth Factor metabolism, Monocytes metabolism, Ischemia pathology, Ischemia metabolism, Ischemia therapy, Neovascularization, Physiologic, Hindlimb blood supply
- Abstract
Despite decades of effort aimed at developing clinically effective cell therapies, including mixed population mononuclear cells, to revascularize the ischemic limb, there remains a paucity of patient-based studies that inform the function and fate of candidate cell types. In this study, we showed that circulating proangiogenic/arteriogenic monocytes (PAMs) expressing the FcγIIIA receptor CD16 were elevated in patients with chronic limb-threatening ischemia (CLTI), and these amounts decreased after revascularization. Unlike CD16-negative monocytes, PAMs showed large vessel remodeling properties in vitro when cultured with endothelial cells and smooth muscle cells and promoted salvage of the ischemic limb in vivo in a mouse model of hindlimb ischemia. PAMs showed a propensity to migrate toward and bind to ischemic muscle and to secrete angiogenic/arteriogenic factors, vascular endothelial growth factor A (VEGF-A) and heparin-binding epidermal growth factor. We instigated a first-in-human single-arm cohort study in which autologous PAMs were injected into the ischemic limbs of five patients with CLTI. Greater than 25% of injected cells were retained in the leg for at least 72 hours, of which greater than 80% were viable, with evidence of enhanced large vessel remodeling in the injected muscle area. In summary, we identified up-regulation of a circulatory PAM subpopulation as an endogenous response to limb ischemia in CLTI and tested a potentially clinically relevant therapeutic strategy.
- Published
- 2024
- Full Text
- View/download PDF
245. Intra-arterial Fractional Flow Reserve Measurements Provide an Objective Assessment of the Functional Significance of Peripheral Arterial Stenoses.
- Author
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Albayati MA, Patel A, Modi B, Saha P, Karim L, Perera D, Smith A, and Modarai B
- Subjects
- Humans, Male, Middle Aged, Aged, Female, Constriction, Pathologic, Coronary Angiography, Pilot Projects, Severity of Illness Index, Predictive Value of Tests, Fractional Flow Reserve, Myocardial physiology, Coronary Stenosis diagnostic imaging, Coronary Stenosis therapy
- Abstract
Objective: Peripheral arterial stenoses (PAS) are commonly investigated with duplex ultrasound (DUS) and angiography, but these are not functional tests. Fractional flow reserve (FFR), a pressure based index, functionally assesses the ischaemic potential of coronary stenoses, but its utility in PAS is unknown. FFR in the peripheral vasculature in patients with limb ischaemia was investigated., Methods: Patients scheduled for angioplasty and or stenting of isolated iliac and superficial femoral artery stenoses were recruited. Resting trans-lesional pressure gradient (P
d /Pa ) and FFR were measured after adenosine provoked hyperaemia using an intra-arterial 0.014 inch flow and pressure sensing wire (ComboWire XT, Philips). Prior to revascularisation, exercise ABPI (eABPI) and DUS derived peak systolic velocity ratio (PSVR) of the index lesion were determined. Calf muscle oxygenation was measured using blood oxygenation level dependent cardiovascular magnetic resonance prior to and after revascularisation., Results: Forty-one patients (32, 78%, male, mean age 65 ± 11 years) with 61 stenoses (iliac 32; femoral 29) were studied. For lesions < 80% stenosis, resting Pd /Pa was not influenced by the degree of stenosis (p = .074); however, FFR was discriminatory, decreasing as the severity of stenosis increased (p = .019). An FFR of < 0.60 was associated with critical limb threatening ischaemia (area under the curve [AUC] 0.87; 95% CI 0.75 - 0.95), in this study performing better than angiographic % stenosis (0.79; 0.63 - 0.89), eABPI (0.72; 0.57 - 0.83), and PSVR (0.65; 0.51 - 0.78). FFR correlated strongly with calf oxygenation (rho, 0.76; p < .001). A greater increase in FFR signalled resolution of symptoms and signs (ΔFFR 0.25 ± 0.15 vs. 0.13 ± 0.09; p = .009) and a post-angioplasty and stenting FFR of > 0.74 predicted successful revascularisation (combined sensitivity and specificity of 95%; AUC 0.98; 0.91 - 1.00)., Conclusion: This pilot study demonstrates that FFR can objectively measure the functional significance of PAS that compares favourably with visual and DUS based assessments. Its role as a quality control adjunct that confirms optimal vessel patency after angioplasty and or stenting also merits further investigation., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
246. HTATIP2 regulates arteriogenic activity in monocytes from patients with limb ischemia.
- Author
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Patel AS, Ludwinski FE, Mondragon A, Nuthall K, Saha P, Lyons O, Squadrito ML, Siow R, De Palma M, Smith A, and Modarai B
- Subjects
- Animals, Mice, Humans, Aged, Collateral Circulation, Muscle, Skeletal metabolism, Mice, Knockout, Ischemia metabolism, Transcription Factors, Acetyltransferases, Monocytes metabolism, Neovascularization, Physiologic
- Abstract
Use of autologous cells isolated from elderly patients with multiple comorbidities may account for the modest efficacy of cell therapy in patients with chronic limb threatening ischemia (CLTI). We aimed to determine whether proarteriogenic monocyte/macrophages (Mo/MΦs) from patients with CLTI were functionally impaired and to demonstrate the mechanisms related to any impairment. Proarteriogenic Mo/MΦs isolated from patients with CLTI were found to have an impaired capacity to promote neovascularization in vitro and in vivo compared with those isolated from healthy controls. This was associated with increased expression of human HIV-1 TAT interactive protein-2 (HTATIP2), a transcription factor known to suppress angiogenesis/arteriogenesis. Silencing HTATIP2 restored the functional capacity of CLTI Mo/MΦs, which was associated with increased expression of arteriogenic regulators Neuropilin-1 and Angiopoietin-1, and their ability to enhance angiogenic (endothelial tubule formation) and arteriogenic (smooth muscle proliferation) processes in vitro. In support of the translational relevance of our findings, silencing HTATIP2 in proarteriogenic Mo/MΦs isolated from patients with CLTI rescued their capacity to enhance limb perfusion in the ischemic hindlimb by effecting greater angiogenesis and arteriogenesis. Ex vivo modulation of HTATIP2 may offer a strategy for rescuing the functional impairment of pro-angio/arteriogenic Mo/MΦs prior to autologous delivery and increase the likelihood of clinical efficacy.
- Published
- 2023
- Full Text
- View/download PDF
247. Investigating Substituent Interactions with Cationic Catalysts.
- Author
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Gong Z, Smith A, Farah AO, Dickerson SD, González-Montiel GA, Laddusaw JM, Cheong PH, and Wiskur SL
- Abstract
Rates of isothiourea catalyzed silylation and acylation reactions were measured for substrates with various electronic substituents at the aryl group. Through these measurements, the intermolecular interactions between cationic catalyst intermediates and different aryl groups were explored. These studies were performed to understand how changes in the catalyst structure affected electrostatic intermolecular interactions. Three different catalysts ( N -methylimidazole and two isothioureas) were employed that varied in their ability to delocalize their cationic nature. The results show that more delocalization on the catalyst reduces the sensitivity to the electronics on the aryl group. Surprisingly, the isothiourea with a fused benzene ring provided additional points of interaction with groups that contained lone-pairs, significantly affecting the overall rate. This work helps explore the interactions that dominate in these types of catalytic systems, to aid in future organocatalysis development. Density functional theory (DFT) studies further confirmed isothiourea/aryl ring interaction with the alcohol substrate in the acylation process, which confirmed these hypotheses. Electron rich or lone-pair bearing functional groups stabilize the cationic catalyst core, thereby stabilizing the transition states and accelerating the reaction. It was also discovered that in one case, the formation of a stable substrate dimer was responsible for its lower reactivity.
- Published
- 2023
- Full Text
- View/download PDF
248. Response to "Re. A Systematic Review of the Safety and Efficacy of Inferior Vena Cava Stenting".
- Author
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Morris RI, Smith A, and Black SA
- Subjects
- Humans, Systematic Reviews as Topic, Vena Cava, Inferior diagnostic imaging, Vena Cava, Inferior surgery
- Published
- 2023
- Full Text
- View/download PDF
249. A Systematic Review of the Safety and Efficacy of Inferior Vena Cava Stenting.
- Author
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Morris RI, Jackson N, Smith A, and Black SA
- Subjects
- Adult, Humans, Male, Female, Middle Aged, Retrospective Studies, Quality of Life, Treatment Outcome, Stents, Vena Cava, Inferior diagnostic imaging, Vena Cava, Inferior surgery, Budd-Chiari Syndrome surgery
- Abstract
Objective: Inferior vena cava (IVC) stenting may provide benefit to patients with symptomatic obstruction; however, there are no devices currently licensed for use in the IVC and systematic reviews on the topic are lacking. The aim of this study was to carry out a systematic review of the literature and meta-analysis to investigate the safety and efficacy of IVC stenting in all adult patient groups., Data Sources: The Medline and Embase databases were searched for studies reporting outcomes for safety and effectiveness of IVC stenting for any indication in series of 10 or more patients., Review Methods: A systematic review of the literature was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Thirty-three studies were included describing 1 575 patients. Indications for stenting were malignant IVC syndrome (229 patients), thrombotic disease (807 patients), Budd-Chiari syndrome (501 patients), and IVC stenosis post liver transplantation (47 patients). The male:female ratio was 2:1 and the median age ranged from 30 to 61 years. The studies included were not suitable for formal meta-analysis as 30/33 were single centre retrospective studies with no control groups and there was considerable inconsistency in outcome reporting. There was significant risk of bias in 94% of studies. Median reported technical success was 100% (range 78 - 100%), primary patency was 75% (38 - 98%), and secondary patency was 91.5% (77 - 100%). Major complications were pulmonary embolism (three cases), stent migration (12 cases), and major bleeding (15 cases), and there were three deaths in the immediate post-operative period. Most studies reported improvement in clinical symptoms but formal reporting tools were not used consistently., Conclusion: The evidence base for IVC stenting consists of predominantly single centre, retrospective, observational studies that have a high risk of bias. Nonetheless the procedure appears safe with few major adverse events, and studies that reported clinical outcomes demonstrate improvement in symptoms and quality of life. Randomised controlled trials and prospective registry based studies with larger patient numbers and standardised outcome are required to improve the evidence base for this procedure., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
250. Performance of Open and Closed Cell Laser Cut Nitinol Stents for the Treatment of Chronic Iliofemoral Venous Outflow Obstruction in Patients Treated at a Single Centre.
- Author
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Morris RI, Jackson N, Khan T, Karunanithy N, Thulasidasan N, Smith A, Black SA, and Saha P
- Subjects
- Adult, Alloys, Female, Humans, Lasers, Male, Retrospective Studies, Stents, Treatment Outcome, Vascular Patency, Iliac Vein diagnostic imaging, Iliac Vein surgery, Vascular Diseases
- Abstract
Objective: A number of dedicated self expanding nitinol stents have been developed for use in the venous system, with both open cell (OC) and closed cell (CC) designs available. Data comparing these different designs are lacking. The objective of this study was to evaluate outcomes in patients treated with open and closed cells for unilateral chronic iliac vein obstruction., Methods: A single centre retrospective cohort study was conducted, including all patients treated with a dedicated nitinol venous stent between 2014 and 2019. Stent patency and details of re-interventions (including lysis, venoplasty, reinforcement, extension, arteriovenous fistula formation) were examined in the first post-operative year. Subgroup analysis described outcomes for patients treated with OC and CC stents ending above the inguinal ligament and those who required extension into the common femoral vein. Cox regression analysis was used to identify factors associated with loss of primary patency., Results: A total of 207 patients were included (OC 100 patients, CC 107 patients). There was no significant difference between the groups for age (OC 42 years, CC 44 years); gender (OC and CC 67% female); presence of post-thrombotic lesions (OC 71%, CC 73%); stenting across the inguinal ligament (OC 58%, CC 56%), or presence of inflow disease (OC 49%, CC 47%). Primary and cumulative patency at 12 months were similar between groups (primary: OC 63%, CC 65%; cumulative: OC 93%, CC 90%). Patients with a CC stent across the inguinal ligament had a greater risk of needing multiple re-interventions at one year compared with those with an OC stent (odds ratio 2.84, 95% confidence interval [CI] 1.16 - 6.9) but overall, the only factor significantly associated with loss of primary patency was inflow vessel disease (hazard ratio 3.39, 95% CI 1.73 - 6.62, p < .001)., Conclusion: OC and CC dedicated nitinol venous stents were observed to perform similarly in terms of patency and symptom improvement at one year. Disease of the inflow vessels was the most important factor associated with a loss of stent patency irrespective of stent design., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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