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Clinical Science (1979-)

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https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#1
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28495910/oxidative-imbalance-and-kidney-damage-in-spontaneously-hypertensive-rats-activation-of-extrinsic-apoptotic-pathway
#2
Daniele La Russa, Elvira Brunelli, Daniela Pellegrino
In both humans and animals, essential hypertension acts as a risk factor for subclinical kidney damage and precedes renal dysfunction. Several lines of evidence indicate that hypertension and oxidative stress are closely related. The increase in vascular oxidative stress plays a key role in the pathophysiological consequences of hypertension, including kidney disease. Our study examined this issue in SHR, a reliable model of essential hypertension. We used SHR 20 weeks-old when hypertension is stably developed, vascular remodeling started, but kidney function is preserved...
May 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28495909/pulse-wave-velocity-is-associated-with-cognitive-impairment-in-hemodialysis-patients
#3
Susanne Angermann, Marcus Baumann, Siegfried Wassertheurer, Christopher Clemens Mayer, Dominik Steubl, Christine Hauser, Yana Suttmann, Anna-Lena Reichelt, Robin Satanovskij, Georg Lorenz, Moritz Lukas, Bernhard Haller, Uwe Heemann, Timo Grimmer, Christoph Schmaderer
BACKGROUND: Cognitive impairment in hemodialysis patients is common and associated with adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore, we examined the potential relationship between cognitive impairment and three different categories of risk factors with particular focus on arterial stiffness measured by Pulse Wave Velocity (PWV). METHODS: A total of 201 chronic hemodialysis patients underwent cognitive testing under standardized conditions using the Montreal Cognitive Assessment (MoCA)...
May 11, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28487471/using-dti-to-assess-white-matter-microstructure-in-cerebral-small-vessel-disease-svd-in-multi-centre-studies
#4
Iain David Croall, Valerie Lohner, Barry Moynihan, Usman Khan, Ahamad Hassan, John T O'Brien, Robin G Morris, Daniel J Tozer, Victoria C Cambridge, Kirsty Harkness, David Werring, Andrew M Blamire, Gary A Ford, Thomas R Barrick, Hugh S Markus
Diffusion tensor imaging (DTI) metrics such as Fractional Anisotropy (FA) and Mean Diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multi-site, further studies are required to determine whether associations with cognition of similar strength can be detected in a multi-centre setting. 109 patients (mean age=68) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across 6 sites as part of the PRESERVE DTI sub-study...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28487470/discrepant-effects-of-heart-failure-on-electrophysiological%C3%A2-property-in-right-ventricular-outflow-tract-and-left-ventricular-outflow-tract-cardiomyocytes
#5
Yen-Yu Lu, Chen-Chuan Cheng, Chin-Feng Tsai, Yung Kuo Lin, Ting-I Lee, Yao-Chang Chen, Shih-Ann Chen, Yi Jen Chen
Ventricular arrhythmias commonly arise from the right and left ventricular outflow tracts (RVOT/LVOT) in patients without structural heart disease. Heart failure (HF) significantly increases the risk of ventricular arrhythmias. The regional differences and how HF affects the electrophysiological characteristics of RVOT and LVOT cardiomyocytes remain unclear. The whole-cell patch clamp technique was used to investigate the action potentials and ionic currents in isolated single RVOT and LVOT cardiomyocytes from control and rapid ventricular pacing-induced HF rabbit...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28487469/phosphoinositide-3-kinase-p110%C3%AE-gene-delivery-limits-diabetes-induced-cardiac-nadph-oxidase-and-cardiomyopathy-in-a-mouse-model-with-established-diastolic-dysfunction
#6
Darnel Prakoso, Miles J DeBlasio, Chengxue Qin, Sarah Rosli, Helen Kiriazis, Hongwei Qian, Xiao-Jun Du, Kate L Weeks, Paul Gregorevic, Julie R McMullen, Rebecca H Ritchie
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterised by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the current study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to mice with established diabetes-induced LV diastolic dysfunction...
May 9, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28468952/reliability-of-an-automatic-classifier-for-brain-enlarged-perivascular-spaces-burden-and-comparison-with-human-performance
#7
Victor Gonzalez-Castro, Maria Del Carmen Valdes-Hernandez, Francesca Chappell, Paul A Armitage, Stephen Makin, Joanna Wardlaw
In the brain, enlarged perivascular spaces (PVS) relate to cerebral small vessel disease, poor cognition, inflammation and hypertension. We propose a fully automatic scheme that uses a support vector machine(SVM) to classify the burden of PVS in the basal ganglia(BG) region as low or high. We assess the performance of three different types of descriptors extracted from the BG region in T2-weighted MRI images: 1)statistics obtained from Wavelet transform's coefficients, 2)local binary patterns and 3)bag of visual words (BoW)-based descriptors characterising local keypoints obtained from a dense grid with the scale-invariant feature transform characteristics...
May 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28468951/insulin-resistance-promotes-lysyl-oxidase-like-2induction-and-fibrosis-accumulation-in-nonalcoholic-fatty-liver-disease
#8
Paola Dongiovanni, Marica Meroni, Guido Alessandro Baselli, Giulia Alessandra Bassani, Raffaela Rametta, Alessandro Pietrelli, Marco Maggioni, Federica Facciotti, Valentina Trunzo, Sara Badiali, Silvia Fargion, Stefano Gatti, Luca Vittorio Carlo Valenti
Background & Aims: In patients with nonalcoholic fatty liver disease (NAFLD), insulin resistance (IR) associates with fibrosis progression independently of hepatic inflammation, but the mechanisms are still unclear. Methods : We modeled the independent contribution of inflammation (steatohepatitis: NASH) by exploiting the methionine-choline deficient (MCD) diet, and that of IR by insulin receptor haploinsufficiency (InsR+/-), in the pathogenesis of liver fibrosis in C57Bl/6 mice. We confirmed study findings in 96 patients with NAFLD...
May 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28468950/er-stress-dependent-microparticles-derived-from-smooth-muscle-cells-promote-endothelial-dysfunction-during-thoracic-aortic-aneurysm-and-dissection
#9
Lixin Jia, Wen-Mei Zhang, Tao-Tao Li, Yan Liu, Chun-Mei Piao, You-Cai Ma, Yu Lu, Yuan Wang, Ting-Ting Liu, Yong-Fen Qi, Jie Du
Vascular smooth muscle cells (SMCs) degeneration is one of the key features of thoracic aortic aneurysm and dissection (TAAD). We and others showed that elevated endoplasmic reticulum (ER) stress causes SMCs loss and TAAD formation, however, mechanism whereby how SMCs dysfunction contributes to intimal damage, leading to TAAD remained to be explored. In the present study, In vitro assay showed elevated mechanical stretch (18% elongation, 3600 cycles/hr) stimulated ER stress response and microparticles (MPs) production from both SMCs and endothelial cells (ECs) in a time-dependent manner...
May 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28442557/high-phosphate-induces-a-pro-inflammatory-response-by-vascular-smooth-muscle-cells-modulation-by-vitamin-d-derivatives
#10
Julio M Martínez-Moreno, Carmen Herencia, Addy Montes de Oca, Juan M Díaz-Tocados, Noemi Vergara, Mª José Gomez, Silvia D López-Argüello, Antonio Camargo, Esther Peralbo-Santaella, Maria E Rodríguez-Ortiz, Antonio Canalejo, Mariano Rodriguez, Juan R Muñoz-Castañeda, Yolanda Almaden
In chronic kidney disease patients, high phosphate (HP) levels are associated to cardiovascular disease, the major cause of morbidity and mortality. Since serum phosphate has been independently correlated with inflammation, the present study aimed to investigate an independent direct effect of HP as a pro-inflammatory factor in VSMCs. A possible modulatory effect of vitamin D was also investigated. The study was performed in an in vitro model of human aortic smooth muscle cells (HASMCs). Incubation of cells in a HP (3...
April 25, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28424290/skin-derived-precursors-from-human-subjects-with-type-2-diabetes-yield-dysfunctional-vascular-smooth-muscle-cells
#11
Sarah Katherina Steinbach, Terrence M Yau, Maral Ouzounian, Husam Abdel-Qadir, Mark Chandy, Thomas Waddell, Mansoor Husain
Objective: Few methods enable molecular and cellular studies of vascular aging or type-2 diabetes (T2D). Here we report a new approach to studying human vascular smooth muscle cell (VSMC) pathophysiology by examining VSMCs differentiated from progenitors found in skin. Approach and Results: Skin-derived precursors (SKPs) were cultured from biopsies (N=164, ~1 cm(2)) taken from the edges of surgical incisions of older adults (N=158; males 72%; mean age 62.7±13 years) undergoing cardiothoracic surgery, and differentiated into VSMCs at high efficiency (>80% yield)...
April 19, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28420676/the-association-between-etanercept-serum-concentration-and-psoriasis-severity-is-highly-age-dependent
#12
Iris Detrez, Kristel Van Steen, Siegfried Segaert, Ann Gils
The association between etanercept serum concentration and psoriasis disease severity is poorly investigated and currently etanercept serum concentration monitoring aiming to optimize psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every three months for a period of one year...
April 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28404768/dj-1-overexpression-restores-ischaemic-post-conditioning-mediated-cardioprotection-in-diabetic-rats-%C3%AF-role-of-autophagy
#13
Bin Zhou, Shaoqing Lei, Rui Xue, Yan Leng, Zhengyuan Xia, Zhong-Yuan Xia
IPO (Ischaemic post-conditioning) is a promising method of alleviating myocardial IR (ischaemia -reperfusion) injury; however, IPO-mediated cardioprotection is lost in diabetic hearts via mechanisms that remain largely unclear. We hypothesized that decreased cardiac expression of DJ-1, a positive modulator of autophagy, compromises the effectiveness of IPO-induced cardioprotection in diabetic rats. Diabetic rats subjected to myocardial IR (30 min of coronary artery occlusion followed by 120 min of reperfusion) exhibited more severe myocardial injury, less cardiac autophagy, lower DJ-1 expression and AMPK (adenosine monophosphate-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway activity than non-diabetic rats...
April 12, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28381600/increased-neutrophil-gelatinase-associated-lipocalin-ngal-promotes-airway-remodelling-in-chronic-obstructive-pulmonary-disease
#14
Yujie Wang, Man Jia, Xiaoyi Yan, Limin Cao, Peter J Barnes, Ian M Adcock, Mao Huang, Xin Yao
Airway remodelling is an important component of chronic obstructive pulmonary disease (COPD). Neutrophil gelatinase-associated lipocalin (NGAL) from neutrophils may drive COPD epithelial-mesenchymal transition (EMT). NGAL expression was quantified in the lungs of COPD patients and bronchoalveolar lavage fluid (BALF) of ozone-treated mice. Reticular basement membrane (RBM) thickness and E-cadherin and α-smooth muscle actin (α-SMA) expression were determined in mice airways. Effects of cigarette smoke extract (CSE) and inflammatory factors on NGAL expression in human neutrophils as well as the effects of NGAL on airway structural cells was assessed...
April 5, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28364044/high-serum-thrombospondin-1-concentration-is-associated-with-slower-abdominal-aortic-aneurysm-growth-and-deficiency-promotes-angiotensin-ii-induced-aneurysm-in-mice
#15
Smriti M Krishna, Saiwang Seto, Roby Jose, Jiaze Li, Joseph V Moxon, Paula Clancy, David J Crossman, Paul E Norman, Theophilus I Emeto, Jonathan Golledge
Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix remodeling. In this study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeat ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration ( Spearman's rho (-)0...
March 31, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28360194/neuronal-nitric-oxide-synthase-derived-hydrogen-peroxide-effect-in-grafts-used-in-human-coronary-bypass-surgery
#16
Patrick Wander Endlich, Rosária Dias Aires, Roberta Lins Gonçalves, Eduardo Damasceno Costa, Janaína de Paula Arantes Ângelo, Lucas Ferreira Alves, Rafaela Fernandes da Silva, Bruno Almeida Rezende, Steyner F Cortes, Virgínia S Lemos
Recently, H2O2 has been identified as the endothelium-dependent hyperpolarizing factor (EDHF), which mediates flow-induced dilation in human coronary arteries. Neuronal nitric oxide synthase (nNOS) is expressed in the cardiovascular system and besides NO, generates H2O2 The role of nNOS-derived H2O2 in human vessels is so far unknown. The present study aimed at investigating the relevance of nNOS/H2O2 signaling in human internal mammary artery (IMA) and saphenous vein (SV), the major conduits used in coronary artery bypass grafting...
March 30, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28348005/vascular-basement-membrane-alterations-and-%C3%AE-amyloid-accumulations-in-an-animal-model-of-cerebral-small-vessel-disease
#17
Friederike Held, Alan W J Morris, Daniel Pirici, Solveig Niklass, Matthew M G Sharp, Cornelia Garz, Anne Assmann, Hans-Jochen Heinze, Frank Schreiber, Roxana Octavia Carare, Stefanie Schreiber
Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated by the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analysed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks 1) the percentage area immunostained for vascular collagen IV and laminin was quantified, 2) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM) and 3) the presence of vascular Aβ was assessed...
March 27, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28341661/vascular-endothelial-growth-factor-a165b-ameliorates-outer-retinal-barrier-and-vascular-dysfunction-in-the-diabetic-retina
#18
Nikita Ved, Richard P Hulse, Samuel M Bestall, Lucy F Donaldson, James W Bainbridge, David Bates
Diabetic retinopathy (DR) is one of the leading causes of blindness in the developed world. Characteristic features of DR are retinal neurodegeneration, pathological angiogenesis and breakdown of both the inner and outer retinal barriers of the retinal vasculature and RPE-choroid respectively. Vascular endothelial growth factor-A (VEGF), a key regulator of angiogenesis and permeability, is the target of most pharmacological interventions of DR. VEGF-A can be alternatively spliced at exon 8 to form 2 families of isoforms, pro- and anti-angiogenic...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28325855/pretreatment-with-aldh2-agonist-alda-1-reduces-intestinal-injury-induced-by-ischemia-and-reperfusion-in-mice
#19
Qiankun Zhu, Guizhen He, Jie Wang, Yukang Wang, Wei Chen
Many studies demonstrate that activation of aldehyde dehydrogenase 2 (ALDH2) is protective against oxidative stress via detoxification of cytotoxic aldehydes and could attenuate cardiac, cerebral, lung, and renal ischemia reperfusion (IR) injuries. However, the effect of ALDH2 in intestinal IR is unknown. This study was to determine whether ALDH2 agonist, Alda-1, could alleviate intestinal injury after gut IR. In a mice model of intestinal IR injury, histological grading, proinflammatory cytokines, oxidative stress, cellular apoptosis, chemokine contents, ALDH2 activity, 4-HNE and MDA were evaluated...
March 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28320782/diabetes-confers-in-vitro-calcific-potential-on-serum-which-associates-with-in-vivo-vascular-calcification
#20
Ashish Patidar, Dhruv K Singh, Shori Thakur, Peter Winocour, Ken Farrington, Anwar Baydoun
Although vascular calcification (VC) is prevalent in type 2 diabetes (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) to serum, enabling it to induce VC outside the disease milieu. We therefore investigated the CP of serum from controls and subjects with T2DM with and without in vivo VC . Samples from 20 healthy controls and 45 age- and sex-matched patients with T2DM with MDRD-eGFR>60mL min(-1) were analysed for CP using rat aortic smooth muscle cells in vitro CT scans of femoral arteries identified individuals with in vivo calcification...
March 20, 2017: Clinical Science (1979-)
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