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Plaque stabilisation

Karina Di Gregoli, Nur Najmi Mohamad Anuar, Rosaria Bianco, Stephen J White, Andrew C Newby, Sarah J George, Jason L Johnson
RATIONALE: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with a number of cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm (AAA) stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates TIMP-3 expression and affects atherosclerosis and aneurysms Methods and Results: Here, we demonstrate that miR-181b was over-expressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms, and correlated with decreased expression of predicted miR-181b targets, TIMP-3 and elastin...
October 18, 2016: Circulation Research
K Wand, K Tetz, I R Fischinger, C P Lohmann, M M Maier, N Feucht
Background: Intravitreal anti-VEGF therapy is the gold standard in the treatment of neovascular age-related macular degeneration (nAMD). In recent literature, the benefit of additional photodynamic therapy (PDT) has been debated. The aim of our study was to compare the functional and structural effects of long-term combination therapy with PDT plus ranibizumab with monotherapy with ranibizumab. Material and Methods: In a retrospective study, patients suffering from nAMD were followed up for at least 42 months...
July 25, 2016: Klinische Monatsblätter Für Augenheilkunde
Dawn H W Lau, Marte Hogseth, Emma C Phillips, Michael J O'Neill, Amy M Pooler, Wendy Noble, Diane P Hanger
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuropathological deposits of amyloid plaques and neurofibrillary tangles comprised of β-amyloid and tau protein, respectively. In AD, tau becomes abnormally phosphorylated and aggregates to form intracellular deposits. However, the mechanisms by which tau exerts neurotoxicity in disease remain unclear. Recent studies have suggested that the presence of tau at synapses may indicate a role in neuronal signalling, which could be disrupted in pathological conditions...
2016: Acta Neuropathologica Communications
Ralph A H Stewart, Lars Wallentin, Jocelyne Benatar, Nicolas Danchin, Emil Hagström, Claes Held, Steen Husted, Eva Lonn, Amanda Stebbins, Karen Chiswell, Ola Vedin, David Watson, Harvey D White
OBJECTIVES: To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease. BACKGROUND: A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk. METHODS: At baseline, 15 482 (97...
July 1, 2016: European Heart Journal
Margaret D Ballantyne, Karine Pinel, Rachel Dakin, Alex T Vesey, Louise Diver, Ruth Mackenzie, Raquel Garcia, Paul Welsh, Naveed Sattar, Graham Hamilton, Nikhil Joshi, Marc R Dweck, Joseph M Miano, Martin W McBride, David E Newby, Robert A McDonald, Andrew H Baker
BACKGROUND: Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology. METHODS AND RESULTS: Using RNA sequencing, we identified >300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor...
May 24, 2016: Circulation
Martin Houde, Louisane Desbiens, Adel Schwertani, Gunnar Pejler, Marc Iglarz, Pedro D'Orléans-Juste
AIMS: To determine the impact of mixed endothelin receptor antagonist and mouse mast cell protease-4 (mMCP-4) in the development of atherosclerosis in the mouse model. MATERIALS AND METHODS: Apolipoprotein E (ApoE) KO mice were crossed with mMCP-4 KO mice to generate ApoE/mMCP-4 double KO mice. Atherosclerosis was induced with a normal- or high-fat diet for 12, 27 or 52weeks. Macitentan (30mg/kg/day), a dual ETA/ETB receptor antagonist, was given orally for 6weeks (27week protocol)...
August 15, 2016: Life Sciences
Lorraine Thong, John MacSharry, Desmond M Murphy
BACKGROUND: Statins have been long known for their lipid-lowering properties however there has been recent interest in their potential to positively influence clinical outcomes in pulmonary disease processes manifesting primarily as airway disorders. OBJECTIVES: We review the potential use of statin therapy in respiratory medicine, with particular emphasis on airway disease. We also explore the possible mechanisms for the observed benefits of statins in conditions of the airway...
2016: Drug Metabolism Letters
Mark F McCarty, James H O'Keefe, James J DiNicolantonio
Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes-some of them attributable to pentoxifylline metabolites-appear to play a mediating role in this regard...
2016: Open Heart
Joseph Shalhoub, Leena E Viiri, Amanda J Cross, Scott M Gregan, David M Allin, Nagore Astola, Ian J Franklin, Alun H Davies, Claudia Monaco
Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours...
May 2, 2016: Thrombosis and Haemostasis
Jia Liu, Lu-Ning Wang
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA)...
2015: Cochrane Database of Systematic Reviews
Stefan Verheye, Lynn Roth, Inge De Meyer, Cor E Van Hove, Daniel Nahon, Domenic Santoianni, John Yianni, Wim Martinet, Maurice Buchbinder, Guido R Y De Meyer
AIMS: In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. METHODS AND RESULTS: Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks...
August 20, 2016: EuroIntervention
Zhitao Li, Xin Sun, Shuyuan Guo, Liping Wang, Tengyu Wang, Chenghai Peng, Wei Wang, Zhen Tian, Ruibo Zhao, Wenwu Cao, Ye Tian
5-Aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively induces the apoptosis of atherogenic macrophages, but whether it can stabilise atherosclerotic plaque in vivo is unclear. Here, we used an animal model to evaluate the effects of ALA-SDT on plaque stabilisation. Sixty rabbits were induced atherosclerotic plaques in the femoral artery with a combination of silastic tube placement with atherogenic diet, and randomly assigned into control (n = 12) and SDT (n = 48) groups. In the SDT group, after intravenous injected with ALA (60 mg/kg) animals underwent the treatment of ultrasound with intensities of 0...
October 2015: Thrombosis and Haemostasis
Vivek Krishna Pulakazhi Venu, Patrizia Uboldi, Ashish Dhyani, Alessandro Patrini, Roberta Baetta, Nicola Ferri, Alberto Corsini, Andrés F Muro, Alberico Luigi Catapano, Giuseppe Danilo Norata
The primary transcript of fibronectin undergoes alternative splicing in the cassette-type EDA and EDB exons and in the IIICs segment to generate different protein isoforms. Human carotid atherosclerotic plaques with a more stable phenotype are enriched with EDA containing fibronectin (FN-EDA). The aim of this study was to investigate the role of EDA containing fibronectin during atherogenesis. Mice constitutively expressing or lacking the EDA domain of fibronectin (EDA+/+ or EDA-/-)were crossed with ApoE-/- or LDL-R-/- mice and fed with a western type diet for 12 weeks...
July 2015: Thrombosis and Haemostasis
Neil Vyas, Saba Al-Hashimi, Wuqaas Munir
An 86-year-old woman underwent penetrating keratoplasty for pseudophakic bullous keratopathy and presented with an acute corneal ulcer thereafter. Examination demonstrated a fluffy white infiltrate and epithelial defect with subsequent endothelial plaque formation and anterior chamber inflammation. The ulcer was cultured, and fortified topical vancomycin and tobramycin were initiated but failed to significantly improve the clinical course. Cultures were ultimately positive for fungus Microcyclosporella mali that responded well to topical natamycin with stabilisation of the ulcer after 6 weeks of topical therapy...
2015: BMJ Case Reports
Jeffrey I Weitz
Acute coronary syndrome (ACS) is a medical emergency. Patients who survive the initial event remain at risk of recurrent cardiovascular events. In most cases, ACS is triggered by thrombosis after rupture of an atherosclerotic plaque. Key to thrombus formation at this site is the generation of thrombin, which not only converts fibrinogen to fibrin but also serves as a potent platelet agonist and induces platelet aggregation at the site of vascular injury. Although dual antiplatelet therapy is more effective for the prevention of recurrent events than aspirin alone after ACS, there remains an approximately 10 % risk of recurrent ischaemic events at one year...
November 2014: Thrombosis and Haemostasis
Yana Dautova, Diana Kozlova, Jeremy N Skepper, Matthias Epple, Martin D Bootman, Diane Proudfoot
Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP) crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC) death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥ 1 µM) reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles...
2014: PloS One
Andrew J S Coats, John M Cruickshank
Central obesity is closely linked to hypertension and type-2 diabetes (DM2) in young/middle-age. In the elderly, systolic hypertension is a reflection of aging/stiff arteries. Diastolic (± systolic) hypertension in young/middle-age is accompanied by increased sympathetic nerve activity, particularly in the presence of the metabolic syndrome or DM2. High beta-receptor density (Bmax) and cyclic AMP (cAMP) levels in human lymphocytes, independent of blood pressure, are associated with a high risk of myocardial infarction (not stroke-risk, which is dependent on blood pressure)...
July 1, 2014: International Journal of Cardiology
Anna Cohen, Mary R Myerscough, Rosemary S Thompson
We present an ODE model which we use to investigate how High Density Lipoproteins (HDL) reduce the inflammatory response in atherosclerosis. HDL causes atherosclerotic plaque stabilisation and regression, and is an important potential marker and prevention target for cardiovascular disease. HDL enables cholesterol efflux from the arterial wall, macrophage and foam cell emigration, and has other athero-protective effects. Our basic inflammatory model is augmented to include several different ways that HDL can act in early atherosclerosis...
May 2014: Bulletin of Mathematical Biology
Jia Liu, Lu-Ning Wang
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowing glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA)...
2014: Cochrane Database of Systematic Reviews
Tarun Dave, J Ezhilan, Hardik Vasnawala, Vinod Somani
Atherosclerosis is characterized by formation of plaques on the inner walls of arteries that threatens to become the leading cause of death worldwide via its sequelae of myocardial infarction and stroke. Endothelial dysfunction leads to cholesterol uptake and accumulation of inflammatory markers within the plaque. The stability of a plaque eventually depends on the balance between vascular smooth muscle cells that stabilize it and the inflammatory cells like macrophages and T lymphocytes that make it prone to rupture...
November 2013: Indian Journal of Endocrinology and Metabolism
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