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Pesquisa : D02.626.151 [Categoria DeCS]
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[PMID]:28947615
[Au] Autor:Kawai T; Takayanagi T; Forrester SJ; Preston KJ; Obama T; Tsuji T; Kobayashi T; Boyer MJ; Cooper HA; Kwok HF; Hashimoto T; Scalia R; Rizzo V; Eguchi S
[Ad] Endereço:From the Cardiovascular Research Center, Department of Physiology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (T. Kawai, T. Takayanagi, S.J.F., K.J.P., T.O., T. Tsuji, T. Kobayashi, M.J.B., H.A.C., R.S., V.R., S.E.); Faculty of Health Sciences, Macau Special Administrative
[Ti] Título:Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) Is Required for Angiotensin II/ß-Aminopropionitrile-Induced Abdominal Aortic Aneurysm.
[So] Source:Hypertension;70(5):959-963, 2017 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Angiotensin II (AngII)-activated epidermal growth factor receptor has been implicated in abdominal aortic aneurysm (AAA) development. In vascular smooth muscle cells (VSMCs), AngII activates epidermal growth factor receptor via a metalloproteinase, ADAM17 (a disintegrin and metalloproteinase domain 17). We hypothesized that AngII-dependent AAA development would be prevented in mice lacking ADAM17 in VSMCs. To test this concept, control and VSMC ADAM17-deficient mice were cotreated with AngII and a lysyl oxidase inhibitor, ß-aminopropionitrile, to induce AAA. We found that 52.4% of control mice did not survive because of aortic rupture. All other surviving control mice developed AAA and demonstrated enhanced expression of ADAM17 in the AAA lesions. In contrast, all AngII and ß-aminopropionitrile-treated VSMC ADAM17-deficient mice survived and showed reduction in external/internal diameters (51%/28%, respectively). VSMC ADAM17 deficiency was associated with lack of epidermal growth factor receptor activation, interleukin-6 induction, endoplasmic reticulum/oxidative stress, and matrix deposition in the abdominal aorta of treated mice. However, both VSMC ADAM17-deficient and control mice treated with AngII and ß-aminopropionitrile developed comparable levels of hypertension. Treatment of C57Bl/6 mice with an ADAM17 inhibitory antibody but not with control IgG also prevented AAA development. In conclusion, VSMC ADAM17 silencing or systemic ADAM17 inhibition seems to protect mice from AAA formation. The mechanism seems to involve suppression of epidermal growth factor receptor activation.
[Mh] Termos MeSH primário: Proteína ADAM17
Aminopropionitrilo/metabolismo
Angiotensina II/metabolismo
Aneurisma da Aorta Abdominal
Hipertensão
Músculo Liso Vascular
[Mh] Termos MeSH secundário: Proteína ADAM17/antagonistas & inibidores
Proteína ADAM17/metabolismo
Animais
Aorta Abdominal/metabolismo
Aorta Abdominal/patologia
Aneurisma da Aorta Abdominal/etiologia
Aneurisma da Aorta Abdominal/metabolismo
Aneurisma da Aorta Abdominal/patologia
Aneurisma da Aorta Abdominal/prevenção & controle
Hipertensão/etiologia
Hipertensão/metabolismo
Hipertensão/prevenção & controle
Camundongos
Camundongos Endogâmicos C57BL
Músculo Liso Vascular/metabolismo
Músculo Liso Vascular/patologia
Proteína-Lisina 6-Oxidase/metabolismo
Proteínas Modificadoras da Atividade de Receptores/metabolismo
Receptor do Fator de Crescimento Epidérmico/metabolismo
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptor Activity-Modifying Proteins); 11128-99-7 (Angiotensin II); 151-18-8 (Aminopropionitrile); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 3.4.24.86 (ADAM17 Protein); EC 3.4.24.86 (Adam17 protein, mouse)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170927
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.09822


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[PMID]:28800626
[Au] Autor:Harlow CR; Wu X; van Deemter M; Gardiner F; Poland C; Green R; Sarvi S; Brown P; Kadler KE; Lu Y; Mason JI; Critchley HOD; Hillier SG
[Ad] Endereço:MRC/University of Edinburgh Centre for Reproductive Health, Edinburgh Medical School, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, United Kingdom.
[Ti] Título:Targeting lysyl oxidase reduces peritoneal fibrosis.
[So] Source:PLoS One;12(8):e0183013, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions. METHODS: Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro. RESULTS: NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro. CONCLUSION: Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.
[Mh] Termos MeSH primário: Aminopropionitrilo/farmacologia
Colágeno/antagonistas & inibidores
Dexametasona/farmacologia
Proteínas da Matriz Extracelular/antagonistas & inibidores
Terapia de Alvo Molecular
Fibrose Peritoneal/prevenção & controle
Proteína-Lisina 6-Oxidase/antagonistas & inibidores
Aderências Teciduais/prevenção & controle
[Mh] Termos MeSH secundário: Cavidade Abdominal/cirurgia
Animais
Colágeno/genética
Colágeno/metabolismo
Epitélio/efeitos dos fármacos
Epitélio/metabolismo
Epitélio/patologia
Proteínas da Matriz Extracelular/genética
Proteínas da Matriz Extracelular/metabolismo
Feminino
Expressão Gênica
Seres Humanos
Interleucina-1alfa/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
MicroRNAs/genética
MicroRNAs/metabolismo
Nanotubos de Carbono/toxicidade
Fibrose Peritoneal/induzido quimicamente
Fibrose Peritoneal/genética
Fibrose Peritoneal/patologia
Cultura Primária de Células
Progesterona/farmacologia
Proteína-Lisina 6-Oxidase/genética
Proteína-Lisina 6-Oxidase/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Aderências Teciduais/induzido quimicamente
Aderências Teciduais/genética
Aderências Teciduais/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Extracellular Matrix Proteins); 0 (IL1A protein, human); 0 (Interleukin-1alpha); 0 (MicroRNAs); 0 (Nanotubes, Carbon); 0 (RNA, Messenger); 149137-54-2 (Lox protein, mouse); 151-18-8 (Aminopropionitrile); 4G7DS2Q64Y (Progesterone); 7S5I7G3JQL (Dexamethasone); 9007-34-5 (Collagen); EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170812
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183013


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[PMID]:28660757
[Au] Autor:Rao G; Bansal S; Law WX; O'Dowd B; Dikanov SA; Oldfield E
[Ad] Endereço:Department of Chemistry and ‡Department of Veterinary Clinical Medicine, University of Illinois , Urbana, Illinois 61801, United States.
[Ti] Título:Pulsed Electron Paramagnetic Resonance Insights into the Ligand Environment of Copper in Drosophila Lysyl Oxidase.
[So] Source:Biochemistry;56(29):3770-3779, 2017 Jul 25.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lysyl oxidase (LOX) is a copper amine oxidase that cross-links collagens and elastin in connective tissue and plays an important role in fibrosis, cancer development, and formation of the "metastatic niche". Despite its important biological functions, the structure of human LOX remains unknown (unlike that of an unrelated LOX, from Pichia pastoris). Here, we expressed active LOX from Drosophila melanogaster, DmLOXL1, a close homologue of human LOX, and characterized it by MS, UV-vis, activity, and inhibition assays. We then used bioinformatics, electron paramagnetic resonance, electron spin-echo envelope modulation, and hyperfine sublevel-correlation (HYSCORE) spectroscopies to probe Cu-ligand bonding finding direct evidence for pH-dependent Cu-His interactions. At pH = 9.3, the spectroscopic data indicated primarily a single His bound to Cu, but at pH = 7.5, there was evidence for a ∼ 1:1 mixture of species containing 1 and 3 His ligands. We then used HYSCORE to probe possible interactions between the LOX inhibitor BAPN (ß-aminopropionitrile; 1-[ C N]cyano-2-aminoethane) and the copper center-finding none. Overall, the results are of interest since they provide new spectroscopic information about the nature of the catalytic site in LOX, an important anticancer drug target.
[Mh] Termos MeSH primário: Cobre/química
Proteínas de Drosophila/química
Proteína-Lisina 6-Oxidase/química
[Mh] Termos MeSH secundário: Aminopropionitrilo/química
Animais
Domínio Catalítico
Drosophila melanogaster
Espectroscopia de Ressonância de Spin Eletrônica
Seres Humanos
Ligantes
Pichia
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drosophila Proteins); 0 (Ligands); 151-18-8 (Aminopropionitrile); 789U1901C5 (Copper); EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00308


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[PMID]:28615322
[Au] Autor:Rodriguez D; Braden BP; Boyer SW; Taketa DA; Setar L; Calhoun C; Maio AD; Langenbacher A; Valentine MT; De Tomaso AW
[Ad] Endereço:Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106.
[Ti] Título:In vivo manipulation of the extracellular matrix induces vascular regression in a basal chordate.
[So] Source:Mol Biol Cell;28(14):1883-1893, 2017 Jul 07.
[Is] ISSN:1939-4586
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated the physical role of the extracellular matrix (ECM) in vascular homeostasis in the basal chordate , which has a large, transparent, extracorporeal vascular network encompassing an area >100 cm We found that the collagen cross-linking enzyme lysyl oxidase is expressed in all vascular cells and that in vivo inhibition using ß-aminopropionitrile (BAPN) caused a rapid, global regression of the entire network, with some vessels regressing >10 mm within 16 h. BAPN treatment changed the ultrastructure of collagen fibers in the vessel basement membrane, and the kinetics of regression were dose dependent. Pharmacological inhibition of both focal adhesion kinase (FAK) and Raf also induced regression, and levels of phosphorylated FAK in vascular cells decreased during BAPN treatment and FAK inhibition but not Raf inhibition, suggesting that physical changes in the vessel ECM are detected via canonical integrin signaling pathways. Regression is driven by apoptosis and extrusion of cells through the basal lamina, which are then engulfed by blood-borne phagocytes. Extrusion and regression occurred in a coordinated manner that maintained vessel integrity, with no loss of barrier function. This suggests the presence of regulatory mechanisms linking physical changes to a homeostatic, tissue-level response.
[Mh] Termos MeSH primário: Colágeno/fisiologia
Matriz Extracelular/metabolismo
[Mh] Termos MeSH secundário: Aminopropionitrilo
Animais
Cordados
Colágeno/metabolismo
Colágeno/ultraestrutura
Proteína-Tirosina Quinases de Adesão Focal/metabolismo
Fosforilação
Proteína-Lisina 6-Oxidase/metabolismo
Transdução de Sinais/efeitos dos fármacos
Quinases raf
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
151-18-8 (Aminopropionitrile); 9007-34-5 (Collagen); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases); EC 2.7.11.1 (raf Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1091/mbc.E17-01-0009


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[PMID]:28538980
[Au] Autor:Kim D; Mecham RP; Trackman PC; Roy S
[Ad] Endereço:Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States 2Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts, United States.
[Ti] Título:Downregulation of Lysyl Oxidase Protects Retinal Endothelial Cells From High Glucose-Induced Apoptosis.
[So] Source:Invest Ophthalmol Vis Sci;58(5):2725-2731, 2017 May 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: To investigate the effect of reducing high glucose (HG)-induced lysyl oxidase (LOX) overexpression and increased activity on retinal endothelial cell apoptosis. Methods: Rat retinal endothelial cells (RRECs) were grown in normal (N) or HG (30 mM glucose) medium for 7 days. In parallel, RRECs were grown in HG medium and transfected with LOX small interfering RNA (siRNA), scrambled siRNA as control, or exposed to ß-aminopropionitrile (BAPN), a LOX inhibitor. LOX expression, AKT activation, and caspase-3 activity were determined by Western blot (WB) analysis and apoptosis by differential dye staining assay. Moreover, to determine whether diabetes-induced LOX overexpression alters AKT activation and promotes apoptosis, changes in LOX expression, AKT phosphorylation, caspase-3 activation, and Bax expression were assessed in retinas of streptozotocin (STZ)-induced diabetic mice and LOX heterozygous knockout (LOX+/-) mice. Results: WB analysis indicated significant LOX overexpression and reduced AKT activation under HG condition in RRECs. Interestingly, when cells grown in HG were transfected with LOX siRNA or exposed to BAPN, the number of apoptotic cells was significantly decreased concomitant with increased AKT phosphorylation. Diabetic mouse retinas exhibited LOX overexpression, decreased AKT phosphorylation, and increased Bax and caspase-3 activation compared to values in nondiabetic mice. In LOX+/- mice, reduced LOX levels were observed with increased AKT activity, and reduced Bax and caspase-3 activity. Furthermore, decreased levels of LOX in the LOX+/- mice was protective against diabetes-induced apoptosis. Conclusions: Findings from this study indicate that preventing LOX overexpression may be protective against HG-induced apoptosis in retinal vascular cells associated with diabetic retinopathy.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Diabetes Mellitus Experimental/prevenção & controle
Retinopatia Diabética/prevenção & controle
Regulação para Baixo
Células Endoteliais/enzimologia
Glucose/farmacologia
Proteína-Lisina 6-Oxidase/metabolismo
[Mh] Termos MeSH secundário: Aminopropionitrilo/farmacologia
Animais
Western Blotting
Caspase 3/metabolismo
Células Cultivadas
Diabetes Mellitus Experimental/enzimologia
Diabetes Mellitus Experimental/patologia
Retinopatia Diabética/enzimologia
Retinopatia Diabética/patologia
Células Endoteliais/patologia
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fosforilação
Proteína-Lisina 6-Oxidase/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-akt/metabolismo
RNA Interferente Pequeno
Ratos
Vasos Retinianos/patologia
Transfecção
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bax protein, rat); 0 (RNA, Small Interfering); 0 (bcl-2-Associated X Protein); 151-18-8 (Aminopropionitrile); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.4.22.- (Casp3 protein, rat); EC 3.4.22.- (Caspase 3); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170525
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-21340


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[PMID]:28274752
[Au] Autor:Lu G; Su G; Davis JP; Schaheen B; Downs E; Roy RJ; Ailawadi G; Upchurch GR
[Ad] Endereço:Department of Surgery, University of Virginia, Charlottesville, Va.
[Ti] Título:A novel chronic advanced stage abdominal aortic aneurysm murine model.
[So] Source:J Vasc Surg;66(1):232-242.e4, 2017 Jul.
[Is] ISSN:1097-6809
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The purpose of this study was to establish a reliable, chronic model of abdominal aortic aneurysm (AAA). METHODS: Wild-type 8-week-old C56BL/6 male mice (n = 120) were equally divided into three groups: (1) BAPN group: 0.2% 3-aminopropionitrile fumarate salt (BAPN) drinking water was provided to mice 2 days before surgery until the end of study. Sham aneurysm induction surgery was performed using 5 µL of heat deactivated elastase. (2) Elastase group: mice were given regular drinking water without BAPN. During aneurysm induction surgery, 5 µL of the active form of elastase (10.3 mg protein/mL, 5.9 U/mg protein) was applied on top of the infrarenal abdominal aorta adventitia for 5 minutes. (3) BAPN+elastase group: mice were given BAPN drinking water and the active form of elastase application, as above. On postoperative days 7, 14, 21, 28, and 100, aortic samples were collected for histology, cytokine array, and gelatin zymography after aortic diameter measurement. RESULTS: Compared with the elastase group, the BAPN+elastase group had a higher AAA formation rate (93% vs 65%; P < .01) with more advanced AAAs (25 of 42 vs 1 of 40 for stage II and III; P < .001). Aneurysms from the BAPN+elastase group demonstrated persistent long-term growth (221.5% ± 36.6%, 285.8% ± 78.6%, and 801% ± 160% on days 21, 28, and 100, respectively; P < .001), with considerable thrombus formation (54%) and rupture (31%) at the advanced stages of AAA development. Cytokine levels (pro-matrix metalloproteinase 9, interleukin-1ß, interleukin-6, chemokine [C-C motif] ligand 5, triggering receptor expressed on myeloid cells 1, monocyte chemotactic protein 1, and tissue inhibitor of metalloproteinase 1) in the BAPN+elastase group were higher than in the elastase group on day 7. After day 7, cytokine levels returned to baseline, with the exception of elevated matrix metalloproteinase 2 activity. By histology, CD3-positive T cells in the BAPN+elastase group were elevated on days 28 and 100. CONCLUSIONS: A combination of oral BAPN administration and periaortic elastase application induced a chronic, advanced-stage AAA with characteristics of persistent aneurysm growth, thrombus formation, and spontaneous rupture. Future studies should use this model, especially for examining tissue remodeling during the late stages of aneurysm development.
[Mh] Termos MeSH primário: Aminopropionitrilo/análogos & derivados
Aorta Abdominal/patologia
Aneurisma da Aorta Abdominal/induzido quimicamente
Elastase Pancreática
[Mh] Termos MeSH secundário: Animais
Aorta Abdominal/metabolismo
Aneurisma da Aorta Abdominal/sangue
Aneurisma da Aorta Abdominal/patologia
Ruptura Aórtica/induzido quimicamente
Doença Crônica
Citocinas/sangue
Dilatação Patológica
Modelos Animais de Doenças
Progressão da Doença
Mediadores da Inflamação/sangue
Masculino
Camundongos Endogâmicos C57BL
Trombose/induzido quimicamente
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Inflammation Mediators); 1119-28-4 (beta-aminopropionitrile fumarate); 151-18-8 (Aminopropionitrile); EC 3.4.21.36 (Pancreatic Elastase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE


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[PMID]:26600407
[Au] Autor:Zhan B; Hu Z; Chen J; Zhu R; Zhao H; Yang J; Zhang Z; Nie R
[Ad] Endereço:Department of Cardio-thoracic Surgery, Xiangyang Central Hospital, Hubei University of Art and Science, Hubei Province, China.
[Ti] Título:KLF15 Overexpression Protects ß-Aminopropionitrile-Induced Aortic Rupture in Rodent Model via Inhibiting Connective Tissue Growth Factor.
[So] Source:Thorac Cardiovasc Surg;65(2):120-125, 2017 Mar.
[Is] ISSN:1439-1902
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:KLF15 (Krüppel-like factor 15) was reported to be involved in a lot of cardiovascular diseases. Little is known about its role in initiation and development of aortic dissection (AD). Samples of the human aorta were collected during AD surgery and aortic valve replacement. Lentivirus was used for in vitro and in vivo KLF15 overexpression in BAPN (ß-aminopropionitrile)-induced rat AD models. The survival times were recorded and compared between the two groups. Autopsy was used for confirming aorta rupture in rat models. qPCR analyses were used for detecting gene expression whereas Western blot and immunostaining were used for detecting protein expression when necessary. KLF15 expression was much lower in the aorta walls of AD group patients than the control group subjects. The survival curve showed that the survival time of AD models was prolonged after KLF15 overexpression. qPCR and Western blot showed that connective tissue growth factors (CTGFs) were significantly downregulated in the rat aortas. After KLF15 overexpression in aortic adventitial fibroblasts, the KLF15 mRNA was increased whereas CTGF and its target gene collagens I and III were downregulated. Immunofluorescence staining also showed a decrease in CTGF, collagen I, and III. Lenti-control did not induce a significant change of KLF15, CTGF, collagen I, and III expressions. KLF15 is involved in the mechanism of AD formation in human. Overexpression of KLF15 can partially rescue the aorta remodeling and AD formation in animal models. Our research highlighted a potential of KLF15 to serve as a new therapy target of AD.
[Mh] Termos MeSH primário: Aminopropionitrilo
Aorta/metabolismo
Aneurisma Aórtico/prevenção & controle
Ruptura Aórtica/prevenção & controle
Fator de Crescimento do Tecido Conjuntivo/metabolismo
Terapia Genética/métodos
Fatores de Transcrição Kruppel-Like/biossíntese
Remodelação Vascular
[Mh] Termos MeSH secundário: Animais
Aorta/patologia
Aneurisma Aórtico/induzido quimicamente
Aneurisma Aórtico/genética
Aneurisma Aórtico/metabolismo
Ruptura Aórtica/induzido quimicamente
Ruptura Aórtica/genética
Ruptura Aórtica/metabolismo
Células Cultivadas
Colágeno Tipo I/metabolismo
Colágeno Tipo III/metabolismo
Dilatação Patológica
Modelos Animais de Doenças
Técnicas de Transferência de Genes
Seres Humanos
Fatores de Transcrição Kruppel-Like/genética
Fatores de Transcrição Kruppel-Like/metabolismo
Masculino
Proteínas Nucleares/metabolismo
Ratos Sprague-Dawley
Transdução de Sinais
Fatores de Tempo
Transfecção
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type I); 0 (Collagen Type III); 0 (Ctgf protein, rat); 0 (KLF15 protein, human); 0 (Klf15 protein, rat); 0 (Kruppel-Like Transcription Factors); 0 (Nuclear Proteins); 139568-91-5 (Connective Tissue Growth Factor); 151-18-8 (Aminopropionitrile)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151125
[St] Status:MEDLINE
[do] DOI:10.1055/s-0035-1566743


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[PMID]:27877081
[Au] Autor:Qi C; Li J; Guo S; Li M; Li Y; Li J; Zhang Q; Zheng L; He X; Zheng X; He Y; Wang L; Wei B
[Ad] Endereço:Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
[Ti] Título:P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness.
[So] Source:Int J Biol Sci;12(11):1289-1297, 2016.
[Is] ISSN:1449-2288
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:P-selectin, a cell adhesion molecule, is an important member of the selectin family. Recent studies have shown that P-selectin deletion inhibits tumor growth in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This study aimed to evaluate whether and how P-selectin affects tumor stiffness in Rip1-Tag2 mice. To explore the role of P-selectin in tissue stiffness, we demonstrated that tumor progression in Rip1-Tag2 mice was correlated with tissue stiffness using immunofluorescence and histological staining. Furthermore, we showed that P-selectin deficiency significantly decreased tissue stiffness by inhibiting lysyl oxidase (LOX) expression. Our experiments involving Rip1-Tag2 mice treated with the LOX inhibitor BAPN showed that BAPN significantly abolished collagen deposition to decrease tumor stiffness and thus inhibit tumor growth. These results indicate that P-selectin deletion significantly decreases tumor stiffness in Rip1-Tag2 mice by inhibiting LOX expression. Further study demonstrated that P-selectin-mediated platelet accumulation increases tissue stiffness mainly by increasing LOX expression and thus promotes tumor growth. Therefore, P-selectin may be an effective therapeutic targeting for treating human insulinomas.
[Mh] Termos MeSH primário: Proteínas Ativadoras de GTPase/metabolismo
Insulinoma/metabolismo
Insulinoma/patologia
Selectina-P/metabolismo
Proteína-Lisina 6-Oxidase/metabolismo
[Mh] Termos MeSH secundário: Aminopropionitrilo/farmacologia
Animais
Colágeno/metabolismo
Imunofluorescência
Proteínas Ativadoras de GTPase/genética
Hidroxiprolina/metabolismo
Insulinoma/genética
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Selectina-P/genética
Proteína-Lisina 6-Oxidase/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (GTPase-Activating Proteins); 0 (P-Selectin); 0 (Ralbp1 protein, mouse); 151-18-8 (Aminopropionitrile); 9007-34-5 (Collagen); EC 1.4.3.13 (Protein-Lysine 6-Oxidase); RMB44WO89X (Hydroxyproline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161124
[St] Status:MEDLINE


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[PMID]:27829073
[Au] Autor:Canelón SP; Wallace JM
[Ad] Endereço:Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
[Ti] Título:ß-Aminopropionitrile-Induced Reduction in Enzymatic Crosslinking Causes In Vitro Changes in Collagen Morphology and Molecular Composition.
[So] Source:PLoS One;11(11):e0166392, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Type I collagen morphology can be characterized using fibril D-spacing, a metric which describes the periodicity of repeating bands of gap and overlap regions of collagen molecules arranged into collagen fibrils. This fibrillar structure is stabilized by enzymatic crosslinks initiated by lysyl oxidase (LOX), a step which can be disrupted using ß-aminopropionitrile (BAPN). Murine in vivo studies have confirmed effects of BAPN on collagen nanostructure and the objective of this study was to evaluate the mechanism of these effects in vitro by measuring D-spacing, evaluating the ratio of mature to immature crosslinks, and quantifying gene expression of type I collagen and LOX. Osteoblasts were cultured in complete media, and differentiated using ascorbic acid, in the presence or absence of 0.25mM BAPN-fumarate. The matrix produced was imaged using atomic force microscopy (AFM) and 2D Fast Fourier transforms were performed to extract D-spacing from individual fibrils. The experiment was repeated for quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Fourier Transform infrared spectroscopy (FTIR) analyses. The D-spacing distribution of collagen produced in the presence of BAPN was shifted toward higher D-spacing values, indicating BAPN affects the morphology of collagen produced in vitro, supporting aforementioned in vivo experiments. In contrast, no difference in gene expression was found for any target gene, suggesting LOX inhibition does not upregulate the LOX gene to compensate for the reduction in aldehyde formation, or regulate expression of genes encoding type I collagen. Finally, the mature to immature crosslink ratio decreased with BAPN treatment and was linked to a reduction in peak percent area of mature crosslink hydroxylysylpyridinoline (HP). In conclusion, in vitro treatment of osteoblasts with low levels of BAPN did not induce changes in genes encoding LOX or type I collagen, but led to an increase in collagen D-spacing as well as a decrease in mature crosslinks.
[Mh] Termos MeSH primário: Aminopropionitrilo/farmacologia
Colágeno Tipo I/ultraestrutura
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Colágeno Tipo I/química
Colágeno Tipo I/efeitos dos fármacos
Expressão Gênica
Técnicas In Vitro
Camundongos
Microscopia de Força Atômica
Osteoblastos/metabolismo
Proteína-Lisina 6-Oxidase/antagonistas & inibidores
Proteína-Lisina 6-Oxidase/metabolismo
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type I); 151-18-8 (Aminopropionitrile); EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0166392


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[PMID]:27644881
[Au] Autor:Wang Y; Zhao ZM; Zhang GX; Yang F; Yan Y; Liu SX; Li SH; Wang GK; Xu ZY
[Ad] Endereço:Institution of Cardiac Surgery, Department of Cardiovascular Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.
[Ti] Título:Dynamic autophagic activity affected the development of thoracic aortic dissection by regulating functional properties of smooth muscle cells.
[So] Source:Biochem Biophys Res Commun;479(2):358-364, 2016 Oct 14.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aortic medial degeneration is the key histopathologic feature of Thoracic aortic dissection (TAD). The aim of this study was to identify the change of autophagic activity in the aortic wall during TAD development, and to explore the roles of autophagy on regulating functional properties of smooth muscle cells (SMCs). Firstly, compared with control group (n = 11), the increased expression of autophagic markers Beclin1 and LC3 was detected in the aortic wall from TAD group (n = 23) by immunochemistry and western blot. We found that more autophagic vacuoles were present in the aortic wall of TAD patients using Transmission electron microscopy. Next, autophagic activity was examined in AD mice model established by ß-aminopropionitrile fumarate (BAPN) and angiotensin II. Immunochemistry proved that autophagic activity was dynamically changed during AD development. Beclin1 and LC3 were detected up-regulated in the aortic wall in the second week after BAPN feeding, earlier than the fragmentation or loss of elastic fibers. When AD occurred in the 4th week, the expression of Beclin1 and LC3 began to decrease, but still higher than the control. Furthermore, autophagy was found to inhibit starvation-induced apoptosis of SMCs. Meanwhile, blockage of autophagy could suppress PDGF-induced phenotypic switch of SMCs. Taken together, autophagic activity was dynamically changed in the aortic wall during TAD development. The abnormal autophagy could regulate the functional properties of aortic SMCs, which might be the potential pathogenesis of TAD.
[Mh] Termos MeSH primário: Aneurisma Dissecante/patologia
Aorta Torácica/patologia
Autofagia
Miócitos de Músculo Liso/metabolismo
[Mh] Termos MeSH secundário: Aminopropionitrilo/análogos & derivados
Aminopropionitrilo/química
Angiotensina II/química
Animais
Aorta Torácica/metabolismo
Apoptose
Beclina-1/metabolismo
Diferenciação Celular
Proliferação Celular
Elasticidade
Seres Humanos
Imuno-Histoquímica
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Microscopia Eletrônica de Transmissão
Proteínas Associadas aos Microtúbulos/metabolismo
Fenótipo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BECN1 protein, human); 0 (Beclin-1); 0 (Microtubule-Associated Proteins); 0 (light chain 3, human); 11128-99-7 (Angiotensin II); 1119-28-4 (beta-aminopropionitrile fumarate); 151-18-8 (Aminopropionitrile)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160921
[St] Status:MEDLINE



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