Search
Showing 961–980 of 2058 publications.
-
Gray, Belinda R.; Klimis, Harry; Inam, Shafqat; Ariyathna, Nilshan; Kumar, Shweta; Bailey, Brian P.; Patel, SanjayObjectives: Radial approach invasive coronary angiography has been shown to be superior to the femoral approach in terms of reducing vascular access complications and improving patient comfort. However, one major limitation has been the perception of higher patient radiation exposure, with guidelines recommending 7mSv as an appropriate average effective dose (E) for routine coronary angiography. Therefore, we sought here to assess differences in radiation exposure between the femoral and radial access routes in patients undergoing diagnostic coronary angiography with or without angioplasty (CA +/- PCI), as performed by two operators, experienced in both techniques. Methods: Consecutive patients (n. =. 870) from July 2011-December 2012, undergoing routine CA +/- PCI at Royal Prince Alfred Hospital, Sydney by two experienced interventional cardiologists were identified. Radiation doses were automatically recorded as dose area products (DAPs) at procedure time and converted into E using a conversion factor of 0.18 mSv/(Gycm2), as validated by the National Radiological Protection Board (NRPB). Results: Of the 870 patients, 598 underwent diagnostic CA (347 femoral, 251 radial); and 272 underwent CA+ PCI (179 femoral, 93 radial). The mean age of the patients was 65. . 12 years and the majority (n. =. 617, 71%) were male. Both groups were well matched with respect to baseline demographics, clinical presentation and angiographic characteristics, though there was an excess of patients with a history of coronary grafts in the femoral group, due to operator preference. In the patients who underwent diagnostic CA, there was no significant difference in the average effective radiation dose for femoral versus radial arterial access (. E=. 7.9. . 8.2 vs. 8.3. . 10.6mSv; p. =. 0.66). Similarly, there was also no difference in average effective radiation dose for femoral versus radial arterial access in patients undergoing CA. +. PCI (. E=. 13.2. . 8.1 vs E=. 14.4. . 8.3 mSv; p. =. 0.26). Conclusion: In our high volume cardiac catheterisation laboratory, radiation doses for routine angiography were near UNSC targets. Patient radiation exposure was comparable between femoral and radial approaches, for both CA and CA +/- PCI. Thus, our results allay concerns that radial cardiac catheterisation might be associated with greater radiation exposure. 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
-
Callaghan, Fraser M.; Karkouri, J.; Broadhouse, Kathryn M.; Evin, Morgane A.; Fletcher, D. F.; Grieve, Stuart M.[No abstract available]
-
Yu, Young; Wise, Steven G.; Celermajer, David S.; Bilek, Marcela M.M.; Ng, Martin K.C.Percutaneous coronary intervention has revolutionized the treatment of coronary artery disease. Successive improvements in implantation techniques, stent materials and design, combined with dual antiplatelet therapy have improved stent safety. However, optimal biocompatibility and long-term effectiveness in the absence of pharmaceutical intervention remains elusive. Drug-eluting stents, introduced to combat in stent restenosis was found to impair endothelial regeneration, increasing thrombotic risk. Innovations in polymer technology and new stent designs have improved but not solved these issues. Despite the drawbacks of drug elution it remains a key component of stent platforms, leaving the need for a truly biocompatible platform with lasting clinical efficacy and safety unmet. This review will examine current stent designs and explore proactive approaches to enhance stent biocompatibility. 2015 Future Medicine Ltd.
-
Wakelin, Edgar A.; Yeo, Giselle C.; Kondyurin, Alexey V.; Davies, Michael J.; McKenzie, David R.; Weiss, Anthony Steven; Bilek, Marcela M.M.Plasma immersion ion implantation (PIII) is used here to improve the surface bioactivity of polyether ether ketone (PEEK) by modifying the chemical and mechanical properties and by introducing radicals. Modifications to the chemical and mechanical properties are characterised as a function of ion fluence (proportional to treatment time) to determine the suitability of the treated surfaces for biological applications. Radical generation increases with treatment time, where treatments greater than 400 seconds result in a high concentration of long-lived radicals. Radical reactions are responsible for oxidation of the surface, resulting in a permanent increase in the polar surface energy. The nano-scale reduced modulus was found to increase with treatment time at the surface from 4.4 to 5.2 GPa. The macromolecular Young's modulus was also found to increase, but by an amount corresponding to the volume fraction of the ion implanted region. The treated surface layer exhibited cracking under cyclical loads, associated with an increased modulus due to dehydrogenation and crosslinking, however it did not show any sign of delamination, indicating that the modified layer is well integrated with the substrate-a critical factor for bioactive surface coatings to be used in-vivo. Protein immobilisation on the PIII treated surfaces was found to saturate after 240 seconds of treatment, indicating that there is room to tune surface mechanical properties for specific applications without affecting the protein coverage. Our findings indicate that the modification of the chemical and mechanical properties by PIII treatments as well as the introduction of radicals render PEEK well suited for use in orthopaedic implantable devices. 2015 SPIE.
-
Wakelin, Edgar A.; Kondyurin, Alexey V.; Wise, Steven G.; McKenzie, David R.; Davies, Michael J.; Bilek, Marcela M.M.Plasma immersion ion implantation (PIII) is used in this study to improve the surface bioactivity of polyether ether ketone (PEEK) by modifying the chemical structure and introducing radicals. The kinetic properties of the treated surface are characterised here, allowing for tuning of the PIII process in order to produce PEEK with optimised bioactivity. The optimum PIII ion fluence for PEEK is determined to be 1 1016 ions/cm2. A model is proposed that accounts for the decay of radicals, nitrogen loss, oxygen incorporation and changes in surface energy within the structure. The model is based on the premise that there is a distribution of local chemical environments produced by PIII. The distribution of chemical environments results in a bioactive surface that has a long shelf life, compatible with clinical needs. 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
Zhao, Wenjing; Sun, Qijian; Guo, Ruichen; Pilowsky, Paul M.Many respiration-related interneurons and motoneurons receive a catecholaminergic input, but the extent and distribution of this input to recurrent laryngeal motoneurons that innervate intrinsic muscles of the larynx are not clear. In the present study, we examined the catecholaminergic input to expiratory laryngeal motoneurons in the caudal nucleus ambiguus by combining intracellular labeling of single identified motoneurons, with immunohistochemistry to reveal tyrosine hydroxylase immunoreactive (catecholaminergic) terminal varicosities. Close appositions were found between the two structures, with 185 close appositions per motoneuron (n=7). Close appositions were more frequently observed on distal rather than proximal dendrites. Axosomatic appositions were not seen. In order to determine the source of this input, microinjections of cholera toxin B subunit (1%, 20 nl) were made into the caudal nucleus ambiguus. Retrogradely labeled neurons, located in the ipsilateral nucleus tractus solitarius and the area postrema, were tyrosine hydroxylase-positive. Our results not only demonstrate details of the extent and distribution of potential catecholamine inputs to the expiratory laryngeal motoneuron, but further indicate that the inputs, at least in part, originate from the dorsomedial medulla, providing a potential anatomical basis for previously reported catecholaminergic effects on the laryngeal adductor reflex. J. Comp. Neurol. 523:381-390, 2015. 2014 Wiley Periodicals, Inc.
-
Evin, Morgane A.; Callaghan, Fraser Maurice; Defrance, Carine; Grieve, Stuart M.; de Care, Alain; Cluzel, Philippe; Redheuil, Alban B.; Kachenoura, N.Left atrium (LA) is a principal site of thrombus formation inducing thromboembolic events, which have been associated with LA low flow velocities. Recent developments in magnetic resonance imaging (MRI) 4D flow analysis enable a non-invasive visualization of LA flow patterns. Our main objective was to investigate modifications of the main vortices in the LA with regards to LA functional indices in 4 patients with atrial fibrillation (AF) and 6 healthy volunteers. Vorticity threshold and Q-criterion indices were computed from the centered vorticity calculation on filtered 4D velocity MRI images. Phasic LA longitudinal strains were computed on cine MRI images using LA feature tracking algorithm. LA dilation in AF came along with a drop in LA longitudinal strains. Best correlations between LA flow and functional changes were found for velocity vs. longitudinal strains corresponding to reservoir and LA contraction phases (r=0.69 and r=0.81, p<0.03). Similarly, the highest correlation was found during LA contraction phase for associations between LA longitudinal strains and Q-criterion (r=0.52). In AF, LA functional changes are tightly associated with flow disorganization during the cardiac cycle especially during LA contraction phase. 2015 CCAL.
-
Sherrah, Andrew G.; Grieve, Stuart M.; Jeremy, Richmond William; Bannon, Paul Gerard; Vallely, Michael P.; Puranik, RajeshThe acute event of thoracic aortic dissection carries with it high mortality and morbidity. Despite optimal initial surgical or medical management strategies, the risk of further complications in the long-term, including aneurysmal dilatation and false lumen (FL) expansion, are not insignificant. Adequate follow-up of such conditions requires dedicated imaging where relevant prognostic indicators are accurately assessed. We perform a systematic review of the literature and report the current evidence for the use of magnetic resonance imaging (MRI) in assessment of chronic aortic dissection. We then make a comparison with traditional imaging modalities including computed tomography and echocardiography. We discuss new ways in which MRI may extend existing aortic assessment, including identification of blood-flow dynamics within the TL and FL using phase-contrast imaging. Copyright 2015 Sherrah, Grieve, Jeremy, Bannon, Vallely and Puranik.
-
Wu, Ben Jing; Shrestha, Sudichhya; Ong, Kwok Leung; Johns, Douglas G.; Hou, Liming; Barter, Philip J.; Rye, Kerry AnneObjective-High-density lipoproteins (HDLs) can potentially protect against atherosclerosis by multiple mechanisms, including enhancement of endothelial repair and improvement of endothelial function. This study asks if increasing HDL levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, enhances endothelial repair and improves endothelial function in New Zealand White rabbits with balloon injury of the abdominal aorta. Approach and Results-New Zealand White rabbits received chow or chow supplemented with 0.07% or 0.14% (wt/wt) des-fluoro-anacetrapib for 8 weeks. Endothelial denudation of the abdominal aorta was carried out after 2 weeks. The animals were euthanized 6 weeks postinjury. Treatment with 0.07% and 0.14% des-fluoro-anacetrapib reduced cholesteryl ester transfer protein activity by 814.9% and 9212%, increased plasma apolipoprotein A-I levels by 1.40.1-fold and 1.50.1-fold, increased plasma HDL-cholesterol levels by 1.80.2-fold and 1.90.1-fold, reduced intimal hyperplasia by 3711% and 5110%, and inhibited vascular cell proliferation by 256.1% and 356.7%, respectively. Re-endothelialization of the injured aorta increased from 436.7% (control) to 696.6% and 767.7% in the 0.07% and 0.14% des-fluoro-anacetrapib-treated animals, respectively. Aortic ring relaxation and guanosine 3?,5?-cyclic monophosphate production in response to acetylcholine were also improved. Incubation of HDLs from the des-fluoro-anacetrapib-treated animals with human coronary artery endothelial cells increased cell proliferation and migration relative to control. These effects were abolished by knockdown of scavenger receptor-B1 and PDZ domain-containing protein 1 and by pharmacological inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt. Conclusions-Increasing HDL levels by inhibiting cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelium in damaged New Zealand White rabbit aortas in an scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner. 2015 American Heart Association, Inc.
-
Kwan, Jair C.; Gao, Ling; Macdonald, Peter Simon; Hicks, MarkBackground: Storage of donor hearts in cardioplegic solutions supplemented with agents that mimic the ischaemic preconditioning response enhanced their post-reperfusion function. The present study examines the minimisation of cell death and activation of pro-survival signalling directed towards maintenance of mitochondrial homeostasis in hearts arrested and stored in two such agents, glyceryl-trinitrate, a nitric oxide donor and cariporide, (a sodium-hydrogen exchange inhibitor). Methods: After baseline functional measurement, isolated working rat hearts were arrested and stored for 6h at 4C in either Celsior, Celsior containing 0.1mg/ml glyceryl-trinitrate, 10?M cariporide or both agents. After reperfusion, function was remeasured. Hearts were then processed for immunoblotting or histology. Results: Necrotic and apoptotic markers present in the Celsior group post-reperfusion were abolished by glyceryl-trinitrate, cariporide or both. Increased phosphorylation of ERK and Bcl2, after reperfusion in groups stored in glyceryl-trinitrate, cariporide or both along with increased phospho-STAT3 levels in the glyceryl-trinitrate/cariporide group correlated with functional recovery. Inhibition of STAT3 phosphorylation blocked recovery. No phospho-Akt increase was seen in any treatment. Conclusions: Activation of signalling pathways that favour mitophagy activation (ERK and Bcl2 phosphorylation) and maintenance of mitochondrial transition pore closure after reperfusion (STAT3 and ERK phosphorylation) were crucial for functional recovery of the donor heart. 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
-
Tan, Joanne Tsui Ming; Ng, Martin K.C.; Bursill, C. A.Angiogenesis is important for postnatal physiological processes including tissue neovascularization in response to an ischaemic injury. Conversely, uncontrolled inflammatory-driven angiogenesis can accelerate atherosclerotic plaque and tumour growth. Angiogenesis-associated diseases are highly prevalent globally, with cardiovascular-related disorders and cancer being the leading causes of mortality worldwide. A vast amount of research has been conducted on the vasculoprotective effects of high-density lipoproteins (HDLs) and while current HDL-raising therapies to date have not yielded the desired benefits clinically, its role in angiogenesis is yet to be fully elucidated. Epidemiological studies report positive correlations between elevated HDL levels and improved prognosis in both ischaemia- and inflammatory-driven pathologies, in which angiogenesis plays a key role. This review focuses on current evidence from epidemiological and prospective studies, coupled with animal models and mechanistic studies that highlight the ability of HDL to conditionally regulate angiogenesis. 2015 Published on behalf of the European Society of Cardiology. All rights reserved.
-
Ong, Kwok Leung; Januszewski, Andrzej S.; OConnell, Rachel; Jenkins, Alicia J.; Xu, Aimin; Sullivan, David R.; Barter, Philip J.; Hung, Weiting; Scott, R. S.; Taskinen, Marja Riitta; Keech, Anthony C.; Rye, Kerry AnneAims/hypothesis: Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes.Methods: Plasma FGF21 levels were measured by ELISA at baseline in 9,697 individuals with type 2 diabetes participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. We assessed the association of FGF21 levels with the incidence of different cardiovascular outcomes over 5years. The primary outcome was total cardiovascular disease (CVD) events and the secondary outcomes were the four individual components: coronary heart disease events, total stroke, CVD mortality and coronary and carotid revascularisation. The tertiary outcome was hospitalisation for angina pectoris.Conclusions/interpretation: Higher baseline plasma FGF21 levels were associated with higher risk of cardiovascular events in patients with type 2 diabetes.Results: Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p < 0.01). The associations remained significant for total CVD events and for coronary and carotid revascularisation after further adjusting for confounding factors, with the HR (95% CI) being 1.28 (1.10, 1.50) and 1.26 (1.01, 1.56), respectively, for the highest tertile compared with the lowest tertile (overall effect p = 0.002 and 0.007, respectively). The addition of FGF21 levels to a model including established CVD risk factors predicting total CVD events led to a non-significant increase in the C-statistic but there was a significant improvement in integrated discrimination and net reclassification. 2014, Springer-Verlag Berlin Heidelberg.
-
Chalmers, Alexander D.; Cohen, Anna; Bursill, C. A.; Myerscough, Mary R.We present here a mathematical model describing the primary mechanisms that drive the early stages of atherosclerosis. This involves the interactions between modified low density lipoprotein (LDL), monocytes/macrophages, cytokines and foam cells. This model suggests that there is an initial inflammatory phase associated with atherosclerotic lesion development and a longer, quasi-static process of plaque development inside the arterial wall that follows the initial transient. We will show results that show how different LDL concentrations in the blood stream and different immune responses can affect the development of a plaque. Through numerical bifurcation analysis, we show the existence of a fold bifurcation when the flux of LDL from the blood is sufficiently high. By analysing the model presented in this paper, we gain a greater insight into this inflammatory response qualitatively and quantitatively. 2015, Springer-Verlag Berlin Heidelberg.
-
Mountford, Jessica K.; Petitjean, Claire; Putra, Harun Wijanarko Kusuma; McCafferty, Jonathan A.; Setiabakti, Natasha M.; Lee, Hannah; Tnesen, Lotte L.; McFadyen, James D.; Schoenwaelder, Simone M.; Eckly, Anita E.; Gachet, Christian; Ellis, Sarah L.; Voss, Anne Kathrin; Dickins, Ross A.; Hamilton, Justin R.; Jackson, Shaun P.PI3KC2? is a broadly expressed lipid kinase with critical functions during embryonic development but poorly defined roles in adult physiology. Here we utilize multiple mouse genetic models to uncover a role for PI3KC2? in regulating the internal membrane reserve structure of megakaryocytes (demarcation membrane system) and platelets (open canalicular system) that results in dysregulated platelet adhesion under haemodynamic shear stress. Structural alterations in the platelet internal membrane lead to enhanced membrane tether formation that is associated with accelerated, yet highly unstable, thrombus formation in vitro and in vivo. Notably, agonist-induced 3-phosphorylated phosphoinositide production and cellular activation are normal in PI3KC2? -deficient platelets. These findings demonstrate an important role for PI3KC2? in regulating shear-dependent platelet adhesion via regulation of membrane structure, rather than acute signalling. These studies provide a link between the open canalicular system and platelet adhesive function that has relevance to the primary haemostatic and prothrombotic function of platelets. 2015 Macmillan Publishers Limited. All rights reserved.
-
Strang, Aart C.; Knetsch, Menno L.W.; Koole, Leo Hendrik; de Winter, Robbert Jan; van der Wal, Allard C.; de Vries, Carlie Jacoba M.; Tak, Paul Peter; Bisoendial, Radjesh J.; Stroes, Erik S.G.; Rotmans, Joris I.Background and Aims: Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits. Materials and Methods: The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents. Results: ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.313.8% versus 23.311.3%, p=0.77) or intima surface area (0.810.62 mm2 vs 0.840.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization. Conclusion: ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo. 2015 Strang et al.
-
Carroll, Luke; Pattison, David I.; Fu, Shanlin; Schiesser, Cart H.; Davies, Michael J.; Hawkins, Clare L.Hypochlorous acid (HOCl) and N-chloramines are produced by myeloperoxidase (MPO) as part of the immune response to destroy invading pathogens. However, MPO also plays a detrimental role in inflammatory pathologies, including atherosclerosis, as inappropriate production of oxidants, including HOCl and N-chloramines, causes damage to host tissue. Low molecular mass thiol compounds, including glutathione (GSH) and methionine (Met), have demonstrated efficacy in scavenging MPO-derived oxidants, which prevents oxidative damage in vitro and ex vivo. Selenium species typically have greater reactivity toward oxidants compared to the analogous sulfur compounds, and are known to be efficient scavengers of HOCl and other hypohalous acids produced by MPO. In this study, we examined the efficacy of a number of sulfur and selenium compounds to scavenge a range of biologically relevant N-chloramines and oxidants produced by both isolated MPO and activated neutrophils and characterized the resulting selenium-derived oxidation products in each case. A dose-dependent decrease in the concentration of each N-chloramine was observed on addition of the sulfur compounds (cysteine, methionine) and selenium compounds (selenomethionine, methylselenocysteine, 1,4-anhydro-4-seleno-L-talitol, 1,5-anhydro-5-selenogulitol) studied. In general, selenomethionine was the most reactive with N-chloramines (k<inf>2</inf> 0.8-3.403 M-1 s-1) with 1,5-anhydro-5-selenogulitol and 1,4-anhydro-4-seleno-L-talitol (k<inf>2</inf> 1.1-6.802 M-1 s-1) showing lower reactivity. This resulted in the formation of the respective selenoxides as the primary oxidation products. The selenium compounds demonstrated greater ability to remove protein N-chloramines compared to the analogous sulfur compounds. These reactions may have implications for preventing cellular damage in vivo, particularly under chronic inflammatory conditions. 2015 Elsevier Inc. All rights reserved.
-
Storkey, Corin M.; Pattison, David I.; Koehler, Jamie A.; Gaspard, Dan S.; Evans, Jeff C.; Hagestuen, Erik D.; Davies, Michael J.Exposure of the naturally-occurring sweetener monatin to light and metal ions results in loss of both parent monatin and total indole (monatin plus monatin lactone/lactam) in mock beverage solutions, with an accompanying decrease in sweetness. In this study potential protective strategies to prevent degradation were investigated. Metal ion chelating resin, or the chelators EDTA and desferrioxamine decreased monatin and indole loss for solutions kept either in darkness or exposed to light. Tannic acid and Chinese bayberry extract both afforded protection, but this did not arise from a light filtering effect. Plastics with defined absorbance characteristics provided protection with this being wavelength dependent; yellow transparent PET plastic was most effective. The contribution of these interventions (metal ion removal/binding; antioxidant; light absorption) was additive, with combinations providing the greatest protective effect against monatin and indole loss. These results indicate that it is possible to minimise monatin degradation by appropriate choices of treatments, additives and container. 2014 Elsevier Ltd. All rights reserved.
-
Kim, Christine H.J.; Mitchell, James B.; Bursill, C. A.; Sowers, Anastasia L.; Thetford, Angela D.; Cook, John A.; Van Reyk, David M.; Davies, Michael J.The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in cell and animal systems. In this study we investigated whether supplementation with TEMPOL inhibits inflammation and atherosclerosis in apoE-/- mice fed a high fat diet (HFD). Methods: ApoE-/- mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice were supplemented with 10mg/g TEMPOL in their food. Plasma samples were analysed for triglycerides, cholesterol, low- and high-density lipoprotein cholesterol, inflammatory cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase, MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells. Results: High fat feeding resulted in marked increases in body mass and plasma lipid levels. Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected, along with an increase in leptin and a decrease in adiponectin. TEMPOL supplementation reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased plaque collagen content, decreased lipid content and increased macrophage numbers. Conclusions: These data indicate that in a well-established model of obesity-associated hyperlipidaemia and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis, hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing obesity, metabolic disorders and increasing atherosclerotic plaque stability. 2015 Elsevier Ireland Ltd.
-
Ismael, Fahd O.; Proudfoot, Julie M.; Brown, Bronwyn E.; Van Reyk, David M.; Croft, Kevin D.; Davies, Michael J.; Hawkins, Clare L.Abstract Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F<inf>2</inf>-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis. 2015 Elsevier Inc. All rights reserved.
-
Machaalani, Rita; Ghazavi, Emma; David, Rona Victoria; Hinton, Tina; Makris, Angela; Hennessy, AnnemarieObjective: The role of the nicotinic acetylcholine receptors (nAChR) in pre-eclampsia is unknown. Given that ACh levels are affected in pre-eclampsia, it has been suggested that compensatory changes in nAChR expression may ensue. This study aimed to determine the effects of pre-eclampsia on the mRNA and protein expression of 12 mammalian nAChR subunits. Methods: Placentas were collected from healthy term pregnancies (n=8) and pregnancies complicated by pre-eclampsia (n=7), both being non-cigarette smoke exposed to rule out any role of nicotine. Using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), 12 subunits (?2, ?3, ?4, ?5, ?6, ?7, ?9, ?1, ?2, ?4, ?, and ?) were able to be studied at the mRNA level, while at the protein level using Western blotting, nine subunits (?2, ?3, ?4, ?5, ?7, ?9, ?1, ?2, and ?) were studied. Results: At the mRNA level, pre-eclamptic placentas showed an increase in ?2 (p=0.003), ?9 (p<0.001), ?1 (p=0.03) and ?2 (p=0.02) subunit expression, while at the protein level, ?7 (p=0.004), ?9 (p=0.02), and ? (p=0.003) subunits were increased compared to controls. Conclusion: Certain nAChR subunits are increased in the pre-eclamptic placenta. Given the absence of cigarette smoking, the changes in expression are hypothesised to be due to the hypoxic environment resulting from the pathophysiology of pre-eclampsia, which subsequently affects endogenous ACh levels, yielding compensatory increases in ?2, ?7, ?9, ?1, ?2, and ? nAChR subunits. 2015 Informa Healthcare USA, Inc.
