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Christelle Sanchez, Gabriel Mazzucchelli, Cécile Lambert, Fanny Comblain, Edwin DePauw, Yves Henrotin
OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degradation but also by other joint tissues modifications like subchondral bone sclerosis. In this study, we used a proteomic approach to compare secretome of osteoblast isolated from sclerotic (SC) or non sclerotic (NSC) area of OA subchondral bone. DESIGN: Secretome was analyzed using differential quantitative and relative label free analysis on nanoUPLC G2 HDMS system. mRNA of the more differentially secreted proteins were quantified by RT-PCR in cell culture from 5 other patients...
2018: PloS One
Prama Pallavi, Marc Pretze, Julio Caballero, Yingchun Li, Björn B Hofmann, Eleni Stamellou, Sarah Klotz, Carmen Wängler, Björn Wängler, Ralf Loesel, Steffen Roth, Bastian Theisinger, Handan Moerz, Uta Binzen, Wolfgang Greffrath, Rolf-Detlef Treede, Martin C Harmsen, Bernhard K Krämer, Mathias Hafner, Benito A Yard, Anna-Isabelle Kälsch
We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for transient receptor potential channels of the vanilloid receptor subtype 1 (TRPV1) activation and inhibition of inflammation. The efficacy of NOD to activate TRPV1 was significantly higher compared to variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted (N-octanoyl tyramine) or the ester functionality consisted of a bulky fatty acid (N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its efficacy which further increased by interchanging the carbonyl and amide groups (ΔNODR)...
March 15, 2018: Journal of Medicinal Chemistry
Danh T Tran, Scott Esckilsen, Jennifer Mulligan, Shikhar Mehrotra, Carl Atkinson, Satish N Nadig
BACKGROUND: Microvascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. Following reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection. Current understanding of this relationship, however, centers on the whole allograft instead of ECs...
March 10, 2018: Transplantation
Xiaowei Wang, Amy Kate Searle, Jan David Hohmann, Ao Leo Liu, Meike-Kristin Abraham, Jathushan Palasubramaniam, Bock Lim, Yu Yao, Maria Wallert, Eefang Yu, Yung-Chih Chen, Karlheinz Peter
Abdominal aortic aneurysm (AAA) is an often deadly disease without medical, non-invasive treatment options. The upregulation of vascular cell adhesion molecule-1 (VCAM-1) on aortic endothelium provides an early target epitope for a novel biotechnological theranostic approach. MicroRNA-126 was used as a therapeutic agent, based on its capability to downregulate VCAM-1 expression in endothelial cells and thereby reduces leukocyte adhesion and exerts anti-inflammatory effects. Ultrasound microbubbles were chosen as carriers, allowing both molecular imaging as well as targeted therapy of AAA...
February 16, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Mónica Muñoz-Vega, Felipe Massó, Araceli Páez, Elizabeth Carreón-Torres, Hector A Cabrera-Fuentes, José Manuel Fragoso, Nonanzit Pérez-Hernández, Laurent O Martinez, Souad Najib, Gilberto Vargas-Alarcón, Óscar Pérez-Méndez
BACKGROUND: Primary cultures endothelial cells have been used as models of endothelial related diseases such atherosclerosis. Biological behavior of primary cultures is donor-dependent and data could not be easily reproducible; endothelial cell lines are emerging options, particularly, human dermal microvascular endothelial cells (HMEC-1), that should be validated to substitute primary cultures for the study of HDL functions. METHODS: Morphology, size and granularity of cells were assessed by phase contrast microscopy and flow cytometry of HMEC-1...
March 9, 2018: Lipids in Health and Disease
J S Lawson, H M Syme, C P D Wheeler-Jones, J Elliott
BACKGROUND: Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1...
March 9, 2018: BMC Veterinary Research
F Santamaria-Martos, I Benítez, C Girón, F Barbé, M A Martínez-García, L Hernández, J M Montserrat, E Nagore, A Martorell-Calatayud, F Campos-Rodriguez, J Corral, V Cabriada, J Abad, O Mediano, M F Troncoso, I Cano-Pumarega, A M Fortuna Gutierrez, T Diaz-Cambriles, M Somoza-Gonzalez, I Almendros, R Farre, D Gozal, M Sánchez-de-la-Torre
The goal of this study was to assess the relationship between the severity of OSA and the levels of carcinogenesis- and tumour growth-related biomarkers, in patients with cutaneous melanoma (CM).This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI); 0-5 events/h), mild-OSA (AHI; 5-15 events/h), and moderate to severe OSA (AHI>15 events/h). Enzyme-linked immunosorbent assays (ELISAs) were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (VEGF, IL8, ICAM-1, VCAM-1), and markers of tumour aggressiveness (S100B, MIA)...
March 9, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Weichen Huang, Mingcheng Huang, Hui Ouyang, Jingwen Peng, Jiang Liang
Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-κB p65 translocation was measured by immunofluorescence...
March 5, 2018: European Journal of Pharmacology
Hongbo Wang, Jiangyan Yin, Yi Guo
Endothelial inflammation caused by tobacco smoking is widely considered as a pathogenic factor in many vascular diseases. Drugs such as atorvastatin were found to be an effective treatment in smoking-dependent vascular diseases, but the underlying mechanism is still unclear. Here, we investigated the mechanism of atorvastatin resisting endothelial inflammation caused by tobacco smoking. Firstly, isolated human umbilical vein endothelial cells (HUVECs) were divided into normal control group, cigarette smoking extract (CSE) group, and atorvastatin (AS)+CSE group...
March 6, 2018: Clinical and Experimental Hypertension: CHE
Maxime Gauberti, Antoine P Fournier, Fabian Docagne, Denis Vivien, Sara Martinez de Lizarrondo
Endothelial cells of the central nervous system over-express surface proteins during neurological disorders, either as a cause, or a consequence, of the disease. Since the cerebral vasculature is easily accessible by large contrast-carrying particles, it constitutes a target of choice for molecular magnetic resonance imaging (MRI). In this review, we highlight the most recent advances in molecular MRI of brain endothelial activation and focus on the development of micro-sized particles of iron oxide (MPIO) targeting adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), P-Selectin and E-Selectin...
2018: Theranostics
Zienab Etwebi, Gavin Landesberg, Kyle Preston, Satoru Eguchi, Rosario Scalia
MPO (myeloperoxidase) is a peroxidase enzyme secreted by activated leukocytes that plays a pathogenic role in cardiovascular disease, mainly by initiating endothelial dysfunction. The molecular mechanisms of the endothelial damaging action of MPO remain though largely elusive. Calpain is a calcium-dependent protease expressed in the vascular wall. Activation of calpains has been implicated in inflammatory disorders of the vasculature. Using endothelial cells and genetically modified mice, this study identifies the µ-calpain isoform as novel downstream signaling target of MPO in endothelial dysfunction...
April 2018: Hypertension
Hai-Yan Peng, Hua-Ping Li, Ming-Qing Li
Recent studies have revealed considerable dysfunction of vascular endothelial cells (VECs) and abnormal expression of microRNA (miR)-137 in women with gestational diabetes mellitus (GDM), and the aim of this study was to clarify the underlying mechanism and possible role of microRNA (miR)-137 in dysfunction of VECs during GDM. We found increased levels of miR-137 in the plasma of GDM women and high-glucose (HG)-exposed HUVECs. Upregulating miR-137 in HUVECs elevated the chemokine (C-C motif) ligand 2 (CCL2) secretion and enhanced the chemotaxis and adhesion of U937 and THP-1 (two human acute monocytic leukemia cell lines) cells to HUVECs in a co-culture system...
March 2, 2018: Microvascular Research
Bianca A Trombetta, Becky C Carlyle, Aaron M Koenig, Leslie M Shaw, John Q Trojanowski, David A Wolk, Joseph J Locascio, Steven E Arnold
OBJECTIVE: Alzheimer's disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress...
2018: PloS One
Yeong-Geun Lee, Seon-A Jang, Kyeong-Hwa Seo, Jung Eun Gwag, Hyoung-Geun Kim, Jung-Hwan Ko, So-Ae Ji, Se-Chan Kang, Dae Young Lee, Nam-In Baek
Six lignans including two new lignans were obtained as the principal components of the Forsythia koreana flowers via silica gel (SiO2 ), octadecyl SiO2 (ODS) as well Sephadex LH-20 column chromatography. In addition to two new lignans, named koreanaside A ((7R,8S,7'R,8'S)-5'-hydroxy-3,3'-dimethoxy-7,7'-diepoxylignan 4-O-β-D-glucopyranoside) and koreanaside B ((7R,8S,7'S,8'R)-9,5',7'-trihydroxy-3,3'-dimethoxy-7,9'-epoxylignan 4-O-β-D-glucopyranoside), four known lignans were identified to be (+)-phylligenin, (-)-epipinoresinol, pinoresinol, and tinosposide A...
March 1, 2018: Chemistry & Biodiversity
Uta Hardt, Anders Larsson, Iva Gunnarsson, Robert M Clancy, Michelle Petri, Jill P Buyon, Gregg J Silverman, Elisabet Svenungsson, Caroline Grönwall
BACKGROUND: Immunoglobulin M (IgM) autoreactivity to malondialdehyde (MDA) protein modifications is part of the natural antibody repertoire in health and may have beneficial functions. In contrast, IgG anti-MDA are increased in chronic inflammation and autoimmunity and may instead have pathogenic properties. METHODS: Herein, we investigated serum IgG anti-MDA levels by enzyme-linked immunosorbent assay (ELISA) in 398 systemic lupus erythematosus (SLE) patients in the Swedish Karolinska SLE cohort and compared these to findings in 225 US SLE patients from New York University and Johns Hopkins University...
February 26, 2018: Arthritis Research & Therapy
Carlee D Ruediger, Bobby John, Sathesh Kumar, Han S Lim, Geetanjali Rangnekar, Kurt C Roberts-Thomson, Glenn D Young, David Chase, Prashanthan Sanders, Scott R Willoughby
BACKGROUND: It has been suggested that ethnicity can make a significant difference to the likelihood of thromboembolic stroke related to atrial fibrillation. Ethnic differences have been shown to alter inflammatory and haemostatic factors; however, this may all be confounded by differences in cardiovascular risk factors between different ethnicity. The impact of different ethnicities on the thrombogenic profile is not known. The aim of this study was to investigate differences in markers of inflammation, endothelial function and tissue remodelling between Caucasian and Indian populations with supraventricular tachycardia (SVT)...
January 2018: Indian Pacing and Electrophysiology Journal
Shuyu Piao, Jun Wan Lee, Harsha Nagar, Saet-Byel Jung, Sujeong Choi, Seonhee Kim, Ikjun Lee, Sung-Min Kim, Nara Shin, Yu Ran Lee, Sang Do Lee, Jin Bong Park, Kaikobad Irani, Minho Won, Gang Min Hur, Byeong Hwa Jeon, Dong Woon Kim, Cuk-Seong Kim
AIMS: CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation...
2018: PloS One
Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot, Sally Beard, Ping Cannon, Roxanne Hastie, Tuong V Nguyen, Natalie K Binder, Stephen Tong, Natalie J Hannan
INTRODUCTION: The discovery of new treatments that prevent or treat preeclampsia would be a major advance. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG) are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. We recently identified metformin and esomeprazole as potential treatments for preeclampsia. Both reduce placental and endothelial secretion of sFlt-1 and soluble endoglin, and reduce endothelial dysfunction...
2018: PloS One
Isabel Quesada, Jimena Cejas, Rodrigo García, Beatriz Cannizzo, Analía Redondo, Claudia Castro
AIM: Perivascular adipose tissue (PVAT) is in intimate contact with the vessel wall and extravascular PVAT-derived inflammatory mediators may adversely influence atherosclerotic plaque formation and stability through outside-to-inside signalling. We sought to investigate the role of PVAT on the atheroma development in an experimental animal model of Metabolic Syndrome (MS) associated with oxidative stress and low-grade inflammatory state. We also studied the effect of Pioglitazone an insulin sensitizer, on the aortic wall and its surrounding PVAT, considering a bi-directional communication between both layers...
February 21, 2018: Cardiovascular Therapeutics
Li Jing, Wang Haitao, Wang Qiong, Zhu Fu, Zhang Nan, Zhang Xuezheng
Early diagnosis and changes associated with atherosclerosis are crucial in clinical medicine. However, atherosclerosis is a multifactorial disease. Asiaticoside (AA), a triterpenoid derived from Centella asiatica, has anti-inflammatory activity. Endothelium-derived nitric oxide is important in modulating vascular tone in a distinct vessel size-dependent manner; it plays a dominant role in conduit arteries and endothelium-dependent hyperpolarisation in resistance vessels. This study evaluated the effects of AA administration on human umbilical endothelial cells with oxidised low-density lipoprotein-induced inflammation...
February 19, 2018: Cytotechnology
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