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Book ; Online: Short \& intermediate distance HVP contributions to muon g-2

Alexandrou, Constantia / Bacchio, Simone / Dimopoulos, Petros / Finkenrath, Jacob / Frezzotti, Roberto / Gagliardi, Giuseppe / Garofalo, Marco / Hadjiyiannakou, Kyriakos / Kostrzewa, Bartosz / Jansen, Karl / Lubicz, Vittorio / Petschlies, Marcus / Sanfilippo, Francesco / Simula, Silvano / Urbach, Carsten / Wenger, Urs

SM (lattice) prediction versus $e^+e^-$ annihilation data

2022

Abstract: We present new lattice results of the ETM Collaboration, obtained from extensive simulations of lattice QCD with dynamical up, down, strange and charm quarks at physical mass values, different volumes and lattice spacings, concerning the SM prediction ... ...

Abstract	We present new lattice results of the ETM Collaboration, obtained from extensive simulations of lattice QCD with dynamical up, down, strange and charm quarks at physical mass values, different volumes and lattice spacings, concerning the SM prediction for the so-called intermediate window (W) and short-distance (SD) contributions to the leading order hadronic vacuum polarization (LO-HVP) term of the muon anomalous magnetic moment, $a_\mu$. Results for $a_{\mu}^{\rm LO-HVP,W}$ and $a_{\mu}^{\rm LO-HVP,SD}$, besides representing a step forward to a complete lattice computation of $a_{\mu}^{\rm LO-HVP}$ and a useful benchmark among lattice groups, are compared here with their dispersive counterparts based on experimental data for $e^+e^-$ into hadrons. The comparison confirms the tension in $a_{\mu}^{\rm LO-HVP,W}$, already noted in 2020 by the BMW Collaboration, while showing no tension in $a_{\mu}^{\rm LO-HVP,SD}$. Comment: Talk given at ICHEP 2022 (6-13 July 2022, Bologna - Italy) - Results here are almost final - Contribution accepted for publication on PoS
Keywords	High Energy Physics - Phenomenology ; High Energy Physics - Lattice
Subject code	530 ; 612
Publishing date	2022-12-20
Publishing country	us
Document type	Book ; Online
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Article ; Online: Lithocholic Acid Hydroxyamide Destabilizes Cyclin D1 and Induces G

Magiera, Katarzyna / Tomala, Marcin / Kubica, Katarzyna / De Cesare, Virginia / Trost, Matthias / Zieba, Bartosz J / Kachamakova-Trojanowska, Neli / Les, Marcin / Dubin, Grzegorz / Holak, Tad A / Skalniak, Lukasz

Cell chemical biology

2017 Volume 24, Issue 4, Page(s) 458–470.e18

Abstract: USP2a is a deubiquitinase responsible for stabilization of cyclin D1, a crucial regulator of cell-cycle progression and a proto-oncoprotein overexpressed in numerous cancer types. Here we report that lithocholic acid (LCA) derivatives are inhibitors of ... ...

Abstract	USP2a is a deubiquitinase responsible for stabilization of cyclin D1, a crucial regulator of cell-cycle progression and a proto-oncoprotein overexpressed in numerous cancer types. Here we report that lithocholic acid (LCA) derivatives are inhibitors of USP proteins, including USP2a. The most potent LCA derivative, LCA hydroxyamide (LCAHA), inhibits USP2a, leading to a significant Akt/GSK3β-independent destabilization of cyclin D1, but does not change the expression of p27. This leads to the defects in cell-cycle progression. As a result, LCAHA inhibits the growth of cyclin D1-expressing, but not cyclin D1-negative cells, independently of the p53 status. We show that LCA derivatives may be considered as future therapeutics for the treatment of cyclin D1-addicted p53-expressing and p53-defective cancer types.
MeSH term(s)	Catalytic Domain ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cyclin D1/antagonists & inhibitors ; Cyclin D1/genetics ; Cyclin D1/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Cycloheximide/chemistry ; Cycloheximide/pharmacology ; Down-Regulation/drug effects ; Endopeptidases/chemistry ; Endopeptidases/genetics ; Endopeptidases/metabolism ; G1 Phase Cell Cycle Checkpoints/drug effects ; Glycogen Synthase Kinase 3 beta/metabolism ; HCT116 Cells ; Humans ; Lithocholic Acid/analogs & derivatives ; Lithocholic Acid/pharmacology ; MCF-7 Cells ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Signal Transduction/drug effects ; Tumor Suppressor Protein p53/deficiency ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Ubiquitin Thiolesterase
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p21 ; Tumor Suppressor Protein p53 ; Cyclin D1 (136601-57-5) ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Lithocholic Acid (5QU0I8393U) ; Cycloheximide (98600C0908) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Endopeptidases (EC 3.4.-) ; USP2 protein, human (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2017-03-23
Publishing country	United States
Document type	Journal Article
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2017.03.002
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Book ; Online: G\'EANT Software Maturity Model

Stanisavljevic, Zarko / Walter, Bartosz / Vukasovic, Maja / Todosijevic, Andrijana / Labedzki, Maciej / Wolski, Marcin

2019

Abstract: G\'EANT project is an example of a large organization with around 30 software projects and ... a novel software maturity model that is designed specifically for G\'EANT software development teams and ...

Abstract	G\'EANT project is an example of a large organization with around 30 software projects and around 20 software development teams. Software development teams consist of many skilled associates coming from all members National Research and Education Networks. Three main issues that are common for all these software development teams and their members are: geographical distribution, scattered manpower percentage, and parallel involvement in other high priority projects in their native organizations. This paper presents a novel software maturity model that is designed specifically for G\'EANT software development teams and aims to address the described issues. Comment: 4 pages, 1 figure. Submitted to TELFOR 2018 conference
Keywords	Computer Science - Software Engineering
Publishing date	2019-03-29
Publishing country	us
Document type	Book ; Online
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Article ; Online: The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways.

Witkowski, Maciej / Pardyak, Laura / Pawlicki, Piotr / Galuszka, Anna / Profaska-Szymik, Magdalena / Plachno, Bartosz J / Kantor, Samuel / Duliban, Michal / Kotula-Balak, Malgorzata

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: ... remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor ...

Abstract	Cryptorchidism in horses is a commonly occurring malformation. The molecular basis of this pathology is not fully known. In addition, the origins of high intratesticular estrogen levels in horses remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor (GPER) and establish histological and biochemical cryptorchid testis status, healthy and cryptorchid horse testes were subjected to scanning electron microscopy analysis, histochemical staining for total protein (with naphthol blue black; NBB), acid content (with toluidine blue O; TBO), and polysaccharide content (with periodic acid-Schiff; PAS). The expression of GPER was analyzed by immunohistochemistry and Western blot. GPER-mediated intracellular cAMP and calcium (Ca2+) signaling were measured immunoenzymatically or colorimetrically. Our data revealed changes in the distribution of polysaccharide content but not the protein and acid content in the cryptorchid testis. Polysaccharides seemed to be partially translocated from the interstitial compartment to the seminiferous tubule compartment. Moreover, the markedly decreased expression of GPER and GPER downstream molecules, cAMP and Ca2+, suggests their potential role in testis pathology. Increased estrogen levels in cryptorchid conditions may be linked to disturbed GPER signaling. We postulate that GPER is a prominent key player in testis development and function and may be used as a new biomarker of horse testis in health and disease.
MeSH term(s)	Animals ; Blotting, Western/methods ; Cryptorchidism/metabolism ; Cryptorchidism/veterinary ; Estrogens/metabolism ; GTP-Binding Proteins/metabolism ; Horse Diseases/metabolism ; Horses ; Immunohistochemistry/methods ; Male ; Microscopy, Electron, Scanning/methods ; Receptors, Estrogen/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Testis/metabolism
Chemical Substances	Estrogens ; Receptors, Estrogen ; Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-07-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22137131
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Article ; Online: The G-Protein-Coupled Membrane Estrogen Receptor Is Present in Horse Cryptorchid Testes and Mediates Downstream Pathways

Maciej Witkowski / Laura Pardyak / Piotr Pawlicki / Anna Galuszka / Magdalena Profaska-Szymik / Bartosz J. Plachno / Samuel Kantor / Michal Duliban / Malgorzata Kotula-Balak

International Journal of Molecular Sciences, Vol 22, Iss 7131, p

2021 Volume 7131

Abstract: ... remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor ...

Abstract	Cryptorchidism in horses is a commonly occurring malformation. The molecular basis of this pathology is not fully known. In addition, the origins of high intratesticular estrogen levels in horses remain obscure. In order to investigate the role of the G-protein-coupled membrane estrogen receptor (GPER) and establish histological and biochemical cryptorchid testis status, healthy and cryptorchid horse testes were subjected to scanning electron microscopy analysis, histochemical staining for total protein (with naphthol blue black; NBB), acid content (with toluidine blue O; TBO), and polysaccharide content (with periodic acid–Schiff; PAS). The expression of GPER was analyzed by immunohistochemistry and Western blot. GPER-mediated intracellular cAMP and calcium (Ca2+) signaling were measured immunoenzymatically or colorimetrically. Our data revealed changes in the distribution of polysaccharide content but not the protein and acid content in the cryptorchid testis. Polysaccharides seemed to be partially translocated from the interstitial compartment to the seminiferous tubule compartment. Moreover, the markedly decreased expression of GPER and GPER downstream molecules, cAMP and Ca2+, suggests their potential role in testis pathology. Increased estrogen levels in cryptorchid conditions may be linked to disturbed GPER signaling. We postulate that GPER is a prominent key player in testis development and function and may be used as a new biomarker of horse testis in health and disease.
Keywords	cryptorchidism ; estrogens ; G protein-coupled receptor ; horse ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: G protein-coupled receptors--recent advances.

Latek, Dorota / Modzelewska, Anna / Trzaskowski, Bartosz / Palczewski, Krzysztof / Filipek, Sławomir

Acta biochimica Polonica

2012 Volume 59, Issue 4, Page(s) 515–529

Abstract: The years 2000 and 2007 witnessed milestones in current understanding of G protein-coupled receptor ... With bound agonists they can form a complex with a suitable G protein, be phosphorylated by kinases or bind ... arrestin. The discovered signaling cascades invoked by arrestin independently of G proteins makes the GPCR ...

Abstract	The years 2000 and 2007 witnessed milestones in current understanding of G protein-coupled receptor (GPCR) structural biology. In 2000 the first GPCR, bovine rhodopsin, was crystallized and the structure was solved, while in 2007 the structure of β(2)-adrenergic receptor, the first GPCR with diffusible ligands, was determined owing to advances in microcrystallization and an insertion of the fast-folding lysozyme into the receptor. In parallel with those crystallographic studies, the biological and biochemical characterization of GPCRs has advanced considerably because those receptors are molecular targets for many of currently used drugs. Therefore, the mechanisms of activation and signal transduction to the cell interior deduced from known GPCRs structures are of the highest importance for drug discovery. These proteins are the most diversified membrane receptors encoded by hundreds of genes in our genome. They participate in processes responsible for vision, smell, taste and neuronal transmission in response to photons or binding of ions, hormones, peptides, chemokines and other factors. Although the GPCRs share a common seven-transmembrane α-helical bundle structure their binding sites can accommodate thousands of different ligands. The ligands, including agonists, antagonists or inverse agonists change the structure of the receptor. With bound agonists they can form a complex with a suitable G protein, be phosphorylated by kinases or bind arrestin. The discovered signaling cascades invoked by arrestin independently of G proteins makes the GPCR activating scheme more complex such that a ligand acting as an antagonist for G protein signaling can also act as an agonist in arrestin-dependent signaling. Additionally, the existence of multiple ligand-dependent partial activation states as well as dimerization of GPCRs result in a 'microprocessor-like' action of these receptors rather than an 'on-off' switch as was commonly believed only a decade ago.
MeSH term(s)	Animals ; Cattle ; Crystallography, X-Ray ; Drug Discovery ; GTP-Binding Proteins/chemistry ; GTP-Binding Proteins/metabolism ; Humans ; Ligands ; Phosphorylation ; Protein Conformation ; Receptors, Adrenergic, beta-2/chemistry ; Receptors, Adrenergic, beta-2/metabolism ; Receptors, G-Protein-Coupled/chemistry ; Receptors, G-Protein-Coupled/metabolism ; Rhodopsin/chemistry ; Rhodopsin/metabolism ; Signal Transduction
Chemical Substances	Ligands ; Receptors, Adrenergic, beta-2 ; Receptors, G-Protein-Coupled ; Rhodopsin (9009-81-8) ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2012-12-18
Publishing country	Poland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	595762-x
ISSN	1734-154X ; 0001-527X
ISSN (online)	1734-154X
ISSN	0001-527X
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Article ; Online: The GG genotype of the -152 G/A vascular endothelial growth factor (VEGF) polymorphism predisposes to hypertension-related chronic kidney disease.

Małkiewicz, Anna / Skrzypkowska, Maria / Słomiński, Bartosz / Siebert, Janusz / Gutknecht, Piotr / Myśliwska, Jolanta

Molecular biology reports

2016 Volume 43, Issue 9, Page(s) 967–975

Abstract: Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated ...

Abstract	Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated with chronic kidney disease and endothelial dysfunction in hypertensive patients. There were 100 healthy volunteers enrolled into the control group. The group of patients was constituted by 99 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. All patients were treated with anti-hypertensive polytherapy. Presented study revealed that the hypertensive patients bearing the GG genotype were characterized by the highest values of diastolic blood pressure and markers of endothelial damage such as Angiogenin, Endostatin, CRP as well as von Willebrandt factor. In addition, higher number of immature endothelial progenitor cells with CD34(+)CD133(+), CD34(+)CD133(-) markers was observed in GG hypertensive carriers while in normotensive individuals no differences were found. Such phenomenon may indicate an increased mobilization of bone-marrow derived endothelial progenitors. It may testify to the preserved compensatory mechanism in chronic kidney disease (CKD) patients until the G3a stage of the disease. Moreover, patients with higher estimated glomerular filtration rate (eGFR) level had lower of vWf and Endostatin values, and higher level of VEGF. Taken together our findings clearly indicate the -152 GG hypertensive carriers as more prone to develop CKD. We can suspect that the VEGF -152 GG genotype is strongly associated with hypertension-dependent CKD.
MeSH term(s)	Adult ; Aged ; Case-Control Studies ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Glomerular Filtration Rate ; Humans ; Hypertension/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Renal Insufficiency, Chronic/genetics ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	VEGFA protein, human ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2016-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-016-4035-6
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Article ; Online: SuperBiHelix method for predicting the pleiotropic ensemble of G-protein-coupled receptor conformations.

Bray, Jenelle K / Abrol, Ravinder / Goddard, William A / Trzaskowski, Bartosz / Scott, Caitlin E

Proceedings of the National Academy of Sciences of the United States of America

2013 Volume 111, Issue 1, Page(s) E72–8

Abstract: There is overwhelming evidence that G-protein-coupled receptors (GPCRs) exhibit several distinct ...

Abstract	There is overwhelming evidence that G-protein-coupled receptors (GPCRs) exhibit several distinct low-energy conformations, each of which might favor binding to different ligands and/or lead to different downstream functions. Understanding the function of such proteins requires knowledge of the ensemble of low-energy configurations that might play a role in this pleiotropic functionality. We earlier reported the BiHelix method for efficiently sampling the (12)(7) = 35 million conformations resulting from 30° rotations about the axis (η) of all seven transmembrane helices (TMHs), showing that the experimental structure is reliably selected as the best conformation from this ensemble. However, various GPCRs differ sufficiently in the tilts of the TMHs that this method need not predict the optimum conformation starting from any other template. In this paper, we introduce the SuperBiHelix method in which the tilt angles (θ, ϕ) are optimized simultaneously with rotations (η) efficiently enough that it is practical and sufficient to sample (5 × 3 × 5)(7) = 13 trillion configurations. This method can correctly identify the optimum structure of a GPCR starting with the template from a different GPCR. We have validated this method by predicting known crystal structure conformations starting from the template of a different protein structure. We find that the SuperBiHelix conformational ensemble includes the higher energy conformations associated with the active protein in addition to those associated with the more stable inactive protein. This methodology was then applied to design and experimentally confirm structures of three mutants of the CB1 cannabinoid receptor associated with different functions.
MeSH term(s)	Algorithms ; Binding Sites ; Computational Biology ; Crystallography, X-Ray ; Humans ; Ligands ; Molecular Docking Simulation/methods ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; Receptor, Adenosine A2A/chemistry ; Receptor, Cannabinoid, CB1/chemistry ; Receptors, Adrenergic, beta-2/chemistry ; Receptors, G-Protein-Coupled/chemistry ; Software
Chemical Substances	Ligands ; Receptor, Adenosine A2A ; Receptor, Cannabinoid, CB1 ; Receptors, Adrenergic, beta-2 ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2013-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1321233111
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Article ; Online: Production and characterization of recombinant protein preparations of Endonuclease G-homologs from yeast, C. elegans and humans.

Kieper, Jana / Lauber, Christiane / Gimadutdinow, Oleg / Urbańska, Anna / Cymerman, Iwona / Ghosh, Mahua / Szczesny, Bartosz / Meiss, Gregor

Protein expression and purification

2010 Volume 73, Issue 1, Page(s) 99–106

Abstract: Nuc1p, CPS-6, EndoG and EXOG are evolutionary conserved mitochondrial nucleases from yeast, Caenorhabditis elegans and humans, respectively. These enzymes play an important role in programmed cell death as well as mitochondrial DNA-repair and ... ...

Abstract	Nuc1p, CPS-6, EndoG and EXOG are evolutionary conserved mitochondrial nucleases from yeast, Caenorhabditis elegans and humans, respectively. These enzymes play an important role in programmed cell death as well as mitochondrial DNA-repair and recombination. Whereas a significant interest has been given to the cell biology of these proteins, in particular their recruitment during caspase-independent apoptosis, determination of their biochemical properties has lagged behind. In part, biochemical as well as structural analysis of mitochondrial nucleases has been hampered by the fact that upon cloning and overexpression in Escherichia coli these enzymes can exert considerable toxicity and tend to aggregate and form inclusion bodies. We have, therefore, established a uniform E. coli expression system allowing us to obtain these four evolutionary related nucleases in active form from the soluble as well as insoluble fractions of E. coli cell lysates. Using preparations of recombinant Nuc1p, CPS-6, EndoG and EXOG we have compared biochemical properties and the substrate specificities of these related nucleases on selected substrates in parallel. Whereas Nuc1p and EXOG in addition to their endonuclease activity exert 5'-3'-exonuclease activity, CPS-6 and EndoG predominantly are endonucleases. These findings allow speculating that the mechanisms of action of these related nucleases in cell death as well as DNA-repair and recombination differ according to their enzyme activities and substrate specificities.
MeSH term(s)	Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/biosynthesis ; Caenorhabditis elegans Proteins/chemistry ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Repair ; Endodeoxyribonucleases/biosynthesis ; Endodeoxyribonucleases/chemistry ; Endodeoxyribonucleases/genetics ; Endodeoxyribonucleases/metabolism ; Endonucleases/biosynthesis ; Endonucleases/chemistry ; Endonucleases/genetics ; Endonucleases/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Humans ; Hydrogen-Ion Concentration ; Mitochondrial Proteins/biosynthesis ; Mitochondrial Proteins/chemistry ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Molecular Sequence Data ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/biosynthesis ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/genetics ; Sequence Alignment ; Spectrometry, Fluorescence
Chemical Substances	Caenorhabditis elegans Proteins ; Cps-6 protein, C elegans ; Mitochondrial Proteins ; Recombinant Proteins ; Saccharomyces cerevisiae Proteins ; DNA (9007-49-2) ; EXOG protein, human (EC 3.1.-) ; Endodeoxyribonucleases (EC 3.1.-) ; Endonucleases (EC 3.1.-) ; endonuclease G (EC 3.1.21.-)
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1055455-5
ISSN	1096-0279 ; 1046-5928
ISSN (online)	1096-0279
ISSN	1046-5928
DOI	10.1016/j.pep.2010.04.001
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Article ; Online: The GA genotype of the -1154 G/A (rs1570360) vascular endothelial growth factor (VEGF) is protective against hypertension-related chronic kidney disease incidence.

Małkiewicz, Anna / Słomiński, Bartosz / Skrzypkowska, Maria / Siebert, Janusz / Gutknecht, Piotr / Myśliwska, Jolanta

Molecular and cellular biochemistry

2016 Volume 418, Issue 1-2, Page(s) 159–165

Abstract: ... in chronic kidney disease (CKD). The purpose of our study was to examine the VEGF -1154 G/A (rs1570360) polymorphism ...

Abstract	Vascular endothelial growth factor (VEGF) is a highly specific mitogen with angiogenic and vascular permeability activities for endothelial cells. VEGF participates in maintaining the renal vasculature integrity. There is no doubt that hypertension accelerates progression to renal dysfunction, resulting in chronic kidney disease (CKD). The purpose of our study was to examine the VEGF -1154 G/A (rs1570360) polymorphism among hypertensive patients with CKD. Additionally markers of endothelial damage have been related to the advancement of CKD. There were 96 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. The patients were treated with an anti-hypertensive polytherapy. Ninety-nine healthy volunteers were enrolled as the control group. Our study revealed that both healthy and hypertensive groups frequencies of the genotypes varied significantly (p = 0.030, χ (2) test). The GA genotype frequency was significantly lower among patients in comparison with healthy. The presence of GA genotype was connected with a decreased risk of hypertension disease (OR = 0.48, p = 0.01). The VEGF -1154 GA carriers have been associated with the lowest values of Endostatin (p = 0.020), Angiogenin (p = 0.040) as well as vWf (p = 0.005). The GA genotype has been characterized by the highest values of eGFR (p = 0.024) and the lowest values of creatinine (p = 0.028) and BUN (p = 0.012). It is evident that the GA genotype of VEGF polymorphism localized at -1154 position is a genetic protective factor for development arterial hypertension and is associated with less progressed CKD.
MeSH term(s)	Adult ; Aged ; Genotype ; Humans ; Hypertension/complications ; Hypertension/epidemiology ; Hypertension/genetics ; Hypertension/physiopathology ; Incidence ; Middle Aged ; Polymorphism, Genetic ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/physiopathology ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	VEGFA protein, human ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2016-07
Publishing country	Netherlands
Document type	Clinical Trial ; Journal Article
ZDB-ID	184833-1
ISSN	1573-4919 ; 0300-8177
ISSN (online)	1573-4919
ISSN	0300-8177
DOI	10.1007/s11010-016-2741-y
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