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Kailash Prasad, Abdullah Sarkar, Mohammad A Zafar, Ahmed Shoker, Hamdi Ei Moselhi, Maryann Tranquilli, Bulat A Ziganshin, John A Elefteriades
BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of thoracic aortic aneurysms (TAAs). Cytokines [Interleukin (IL)-Iβ, IL-2, IL-6, and TNF-α)] increase the expression of MMP-2 and -3. Advanced glycation end products (AGEs) interact with cell receptors to increase the release of cytokines. Circulating soluble receptors for AGEs (sRAGE) and endogenous secretory RAGE (esRAGE) compete with membrane bound RAGE for binding with AGEs and reduce the production of cytokines...
February 2016: Aorta (Stamford, Conn.)
Suzanne Miller, Amanda P Henry, Emily Hodge, Alexander K Kheirallah, Charlotte K Billington, Tracy L Rimington, Sangita K Bhaker, Ma'en Obeidat, Erik Melén, Simon K Merid, Caroline Swan, Catherine Gowland, Carl P Nelson, Ceri E Stewart, Charlotte E Bolton, Iain Kilty, Anders Malarstig, Stuart G Parker, Miriam F Moffatt, Andrew J Wardlaw, Ian P Hall, Ian Sayers
INTRODUCTION: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model...
2016: PloS One
Jan Filipovsky, Jitka Seidlerova, Otto Mayer, Petra Karnosova
OBJECTIVE: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. DESIGN AND METHOD: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study ("Post-MONICA")...
September 2016: Journal of Hypertension
Kailash Prasad, Shuchita Tiwari
Advanced glycation end products (AGEs) are heterogeneous group of molecules formed from non-enzymatic reaction of reducing sugars with amino group of proteins, lipids, and nucleic acid. Interaction of AGEs with its cell-bound receptor (RAGE) results in generation of oxygen radicals, nuclear factor kappa-β, pro-inflammatory cytokines and cell adhesion molecules, and is involved in the pathophysiology of cardiovascular diseases (CVD). Circulating soluble forms of RAGE (sRAGE) and endo-secretory RAGE (esRAGE) compete with RAGE for ligand binding and function as a decoy...
October 6, 2016: Current Pharmaceutical Design
Kailash Prasad, Indu Dhar, Qifeng Zhou, Hamdi Elmoselhi, Muhammad Shoker, Ahmed Shoker
Interaction of advanced glycation end products (AGEs) with its cell-bound receptor (RAGE) results in cell dysfunction through activation of nuclear factor kappa-B, increase in expression and release of inflammatory cytokines, and generation of oxygen radicals. Circulating soluble receptors, soluble receptor (sRAGE), endogenous secretory receptor (esRAGE) and cleaved receptor (cRGAE) act as decoy for RAGE ligands and thus have cytoprotective effects. Low levels of sRAGE and esRAGE have been proposed as biomarkers for many diseases...
October 6, 2016: Molecular and Cellular Biochemistry
Xu Wu, Wenyu Gu, Huan Lu, Chengying Liu, Biyun Yu, Hui Xu, Yaodong Tang, Shanqun Li, Jian Zhou, Chuan Shao
Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis...
2016: Oxidative Medicine and Cellular Longevity
Simon D Pouwels, Wouter H van Geffen, Marnix R Jonker, Huib A M Kerstjens, Martijn C Nawijn, Irene H Heijink
Previously, we observed increased serum levels of damage-associated molecular patterns (DAMPs) during COPD exacerbations. Here, gene expression of DAMP receptors was measured in peripheral blood neutrophils of COPD patients during stable disease and severe acute exacerbation. The expression of toll-like receptor (TLR)2, TLR4 and NLR family, pyrin domain-containing 3 (NLRP3) was significantly increased, while serum levels of the soluble form of the decoy receptor for advanced glycation end-product (sRAGE) were decreased during exacerbation...
September 27, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
H R Nejabati, A Mota, L Farzadi, M Ghojazadeh, A Fattahi, K Hamdi, M Nouri
PURPOSE: Considering potential roles of soluble receptor for advanced glycation end products (sRAGE) and placental growth factor (PlGF) in ovarian function and embryo implantation, in the present study we have evaluated the association of these factors and also PlGF/sFlt-1 ratio with the ovarian response and implantation rate by dividing patients according to the OSI. METHODS: In a cross-sectional study, 90 infertile women who were undergoing ICSI cycle using long protocol were recruited...
September 23, 2016: Journal of Endocrinological Investigation
Jan Filipovsky, Jitka Seidlerova, Otto Mayer, Petra Karnosova
OBJECTIVE: Accumulation of advanced glycation end-products (AGE) has been suggested to be involved in several pathophysiological processes in the vessel wall. Soluble isoform of receptor for AGE (sRAGE) acts as a decoy for capturing circulating AGE, thus preventing them from binding to the cell-surface receptor (RAGE) and protecting against the RAGE-AGE axis-elicited processes. We hypothesized that low sRAGE levels might be associated with increased arterial stiffness. DESIGN AND METHOD: In a cross-sectional design, we analyzed 1077 subjects, aged 25 to 64 years, from the Czech population-based study ("Post-MONICA")...
September 2016: Journal of Hypertension
Mitsuhiro Miyashita, Takuo Watanabe, Tomoe Ichikawa, Kazuya Toriumi, Yasue Horiuchi, Akiko Kobori, Itaru Kushima, Ryota Hashimoto, Motoyuki Fukumoto, Shinsuke Koike, Hiroshi Ujike, Tadao Arinami, Yoshitaka Tatebayashi, Kiyoto Kasai, Masatoshi Takeda, Norio Ozaki, Yuji Okazaki, Takeo Yoshikawa, Naoji Amano, Shinsuke Washizuka, Hiroshi Yamamoto, Toshio Miyata, Masanari Itokawa, Yasuhiko Yamamoto, Makoto Arai
Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects...
October 21, 2016: Biochemical and Biophysical Research Communications
Marita Liebisch, Tzvetanka Bondeva, Sybille Franke, Stephan Hause, Gunter Wolf
BACKGROUND: Growth arrest specific 2-like protein 1 (GAS2L1) protein is a member of the GAS2 family of proteins, known to regulate apoptosis and cellular cytoskeleton reorganization in different cells. Recently we identified that Gas2l1 gene expression in podocytes is influenced by advanced glycation end product-bovine serum albumin(AGE-BSA). METHODS: The study was performed employing cultured podocytes and diabetic (db/db) mice, a model of type 2 diabetes. Akbuminuria as wellas urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion as measured with specific ELISAs...
September 16, 2016: Nephrology, Dialysis, Transplantation
Terase F Lancefield, Sheila K Patel, Melanie Freeman, Elena Velkoska, Bryan Wai, Piyush M Srivastava, Mark Horrigan, Omar Farouque, Louise M Burrell
OBJECTIVE: Upregulation of the receptor for advanced glycation end products (RAGE) has been proposed as a pathophysiological mechanism underlying the development of atrial fibrillation (AF). We sought to investigate if soluble RAGE levels are associated with AF in Caucasian patients. METHODS: Patients (n = 587) were prospectively recruited and serum levels of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) measured. The patients included 527 with sinus rhythm, 32 with persistent AF (duration >7 days, n = 32) and 28 with paroxysmal AF (duration <7 days, n = 28)...
2016: PloS One
Matthieu Jabaudon, Pierre Boucher, Etienne Imhoff, Russell Chabanne, Jean-Sébastien Faure, Laurence Roszyk, Sandrine Thibault, Raiko Blondonnet, Gael Clairefond, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Thomas Godet, Bruno Pereira, Vincent Sapin, Jean-Etienne Bazin, Emmanuel Futier, Jean-Michel Constantin
RATIONALE: Sevoflurane improves gas exchange, reduces alveolar edema and inflammation in preclinical studies of lung injury but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS). OBJECTIVES: To assess whether sevoflurane would improve gas exchange and inflammation in ARDS. METHODS: We did a parallel, open-label single center randomized controlled trial at 3 intensive care units from a french university hospital between April, 2014, and February, 2016...
September 9, 2016: American Journal of Respiratory and Critical Care Medicine
Rafał Rzepka, Barbara Dołęgowska, Aleksandra Rajewska, Daria Sałata, Marta Budkowska, Sebastian Kwiatkowski, Andrzej Torbé
Preterm birth remains the most prevalent cause of neonatal morbidity. This study aimed to evaluate the diagnostic value of SDF-1α, resistin, secretory RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) in preterm labor. A total of 211 pregnant women participated in the study. Group A contained 72 women between 22 and 36 weeks of gestation, with premature labor, who finally had preterm birth. Group B contained 66 women in labor between 37 and 41 weeks of gestation. Women in group A had lower SDF-1α and sRAGE levels than those in group B...
2016: BioMed Research International
Barry W Festoff, Ravi K Sajja, Patrick van Dreden, Luca Cucullo
BACKGROUND: The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer's disease (AD) that precedes the hallmarks of amyloid beta (amyloid β) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive...
2016: Journal of Neuroinflammation
Luis C Berrocal-Almanza, Surabhi Goyal, Abid Hussain, Tilman E Klassert, Dominik Driesch, Zarko Grozdanovic, Gadamm Sumanlatha, Niyaz Ahmed, Vijayalakshmi Valluri, Melanie L Conrad, Nickel Dittrich, Ralf R Schumann, Birgit Lala, Hortense Slevogt
Pulmonary tuberculosis (PTB) results in lung functional impairment and there are no surrogate markers to monitor the extent of lung involvement. We investigated the clinical significance of S100A12 and soluble receptor for advanced glycation end-products (sRAGE) for predicting the extent of lung involvement. We performed an observational study in India with 119 newly diagnosed, treatment naïve, sputum smear positive, HIV-negative PTB patients and 163 healthy controls. All patients were followed-up for six months...
2016: Scientific Reports
Wei Sun, Katerina Kechris, Sean Jacobson, M Bradley Drummond, Gregory A Hawkins, Jenny Yang, Ting-Huei Chen, Pedro Miguel Quibrera, Wayne Anderson, R Graham Barr, Patricia V Basta, Eugene R Bleecker, Terri Beaty, Richard Casaburi, Peter Castaldi, Michael H Cho, Alejandro Comellas, James D Crapo, Gerard Criner, Dawn Demeo, Stephanie A Christenson, David J Couper, Jeffrey L Curtis, Claire M Doerschuk, Christine M Freeman, Natalia A Gouskova, MeiLan K Han, Nicola A Hanania, Nadia N Hansel, Craig P Hersh, Eric A Hoffman, Robert J Kaner, Richard E Kanner, Eric C Kleerup, Sharon Lutz, Fernando J Martinez, Deborah A Meyers, Stephen P Peters, Elizabeth A Regan, Stephen I Rennard, Mary Beth Scholand, Edwin K Silverman, Prescott G Woodruff, Wanda K O'Neal, Russell P Bowler
Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs)...
August 2016: PLoS Genetics
John H Meertens, Hans L Nienhuis, Joop D Lefrandt, Casper G Schalkwijk, Kristiina Nyyssönen, Jack J M Ligtenberg, Andries J Smit, Jan G Zijlstra, D J Mulder
BACKGROUND: Advanced glycation end products (AGEs) have been implicated in multiple organ failure, predominantly via their cellular receptor (RAGE) in preclinical studies. Little is known about the time course and prognostic relevance of AGEs in critically ill human patients, including those with severe sepsis. OBJECTIVE: 1) To explore the reliability of Skin Autofluorescence (AF) as an index of tissue AGEs in ICU patients, 2) to compare its levels to healthy controls, 3) to describe the time course of AGEs and influencing factors during ICU admission, and 4) to explore their association with disease severity, outcome, and markers of oxidative stress and inflammation...
2016: PloS One
Jing Xue, Michaele Manigrasso, Matteo Scalabrin, Vivek Rai, Sergey Reverdatto, David S Burz, Daniele Fabris, Ann Marie Schmidt, Alexander Shekhtman
The weak oligomerization exhibited by many transmembrane receptors has a profound effect on signal transduction. The phenomenon is difficult to characterize structurally due to the large sizes of and transient interactions between monomers. The receptor for advanced glycation end products (RAGE), a signaling molecule central to the induction and perpetuation of inflammatory responses, is a weak constitutive oligomer. The RAGE domain interaction surfaces that mediate homo-dimerization were identified by combining segmental isotopic labeling of extracellular soluble RAGE (sRAGE) and nuclear magnetic resonance spectroscopy with chemical cross-linking and mass spectrometry...
September 6, 2016: Structure
Elena Dozio, Silvia Briganti, Alessandra Delnevo, Elena Vianello, Federica Ermetici, Francesco Secchi, Francesco Sardanelli, Lelio Morricone, Alexis E Malavazos, Massimiliano M Corsi Romanelli
PURPOSE: Soluble receptor for advanced glycation end products (sRAGE) is a decoy receptor which sequesters RAGE ligands and acts as a cytoprotective agent. To date, it is unclear whether the lower sRAGE levels observed in obesity are a marker of increased overall adiposity or reflect increases in particular fat depots. Therefore, we evaluated in healthy women the relationship among sRAGE and indicators of adiposity, including abdominal visceral (VAT) and epicardial visceral (EAT) adipose tissues, to explore the potential role of sRAGE as an earlier biomarker of cardiometabolic risk...
August 13, 2016: European Journal of Nutrition
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