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[PMID]:29262278
[Au] Autor:O'Donnell CPF
[Ad] Endereço:From the National Maternity Hospital, the National Children's Research Centre, and the School of Medicine, University College Dublin - all in Dublin, Ireland.
[Ti] Título:The Timing of Cord Clamping for Preterm Infants.
[So] Source:N Engl J Med;377(25):2488-2489, 2017 12 21.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Recém-Nascido Prematuro
[Mh] Termos MeSH secundário: Constrição
Seres Humanos
Recém-Nascido
Fatores de Tempo
[Pt] Tipo de publicação:EDITORIAL; COMMENT
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171222
[Lr] Data última revisão:
171222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171221
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMe1714522


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[PMID]:28832798
[Au] Autor:Huseyin S; Guclu O; Yüksel V; Erkul GSA; Can N; Turan FN; Canbaz S
[Ad] Endereço:Department of Cardiovascular Surgery of Trakya University School of Medicine, Edirne, Turkey.
[Ti] Título:Avoiding Liver Injury with Papaverine and Ascorbic Acid Due to Infrarenal Cross-Clamping: an Experimental Study.
[So] Source:Braz J Cardiovasc Surg;32(3):197-201, 2017 May-Jun.
[Is] ISSN:1678-9741
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Objective:: Ischemia-reperfusion injury after acute ischemia treatment is a serious condition with high mortality and morbidity. Ischemia-reperfusion injury may result in organ failure particularly in kidney, lung, liver, and heart. In our study, we investigated the effects of papaverine and vitamin C on ischemia-reperfusion injury developed in the rat liver after occlusion-reperfusion of rat aorta. Methods:: 32 Sprague-Dawley female rats were randomized into four groups (n=8). Ischemia was induced with infrarenal aortic cross-clamping for 60 minutes; then the clamp was removed and reperfusion was allowed for 120 minutes. While the control group and the ischemia-reperfusion group did not receive any supplementary agent, two other groups received vitamin C and papaverine hydrochloride (papaverine HCL). Liver tissues were evaluated under the light microscope. Histopathological examination was assessed by Suzuki's criteria and results were compared between groups. Results:: In ischemia-reperfusion group, severe congestion, severe cytoplasmic vacuolization, and parenchymal necrosis over 60% (score 4) were observed. In vitamin C group, mild congestion, mild cytoplasmic vacuolization and parenchymal necrosis below 30% (score 2) were found. In papaverine group, moderate congestion, moderate cytoplasmic vacuolization and parenchymal necrosis below 60% (score 3) were observed. Conclusion:: An ischemia of 60 minutes induced on lower extremities causes damaging effects on hepatic tissue. Vitamin C and papaverine are helpful in reducing liver injury after acute ischemia reperfusion and may partially avoid related negative conditions.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Ácido Ascórbico/farmacologia
Fígado/irrigação sanguínea
Fígado/efeitos dos fármacos
Papaverina/farmacologia
Traumatismo por Reperfusão/prevenção & controle
Vasodilatadores/farmacologia
[Mh] Termos MeSH secundário: Animais
Antioxidantes/uso terapêutico
Aorta Abdominal
Ácido Ascórbico/uso terapêutico
Constrição
Modelos Animais de Doenças
Feminino
Fígado/patologia
Necrose
Papaverina/uso terapêutico
Distribuição Aleatória
Ratos Sprague-Dawley
Traumatismo por Reperfusão/patologia
Reprodutibilidade dos Testes
Fatores de Tempo
Resultado do Tratamento
Vasodilatadores/uso terapêutico
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Vasodilator Agents); DAA13NKG2Q (Papaverine); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE


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[PMID]:28683996
[Au] Autor:Halbreiner MS; Yamashita M; Plichta R; Svensson LG
[Ad] Endereço:Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio.
[Ti] Título:An Alternative Technique for Hemiarch Replacement Without Using Deep Hypothermic Circulatory Arrest.
[So] Source:Semin Thorac Cardiovasc Surg;29(1):47-48, 2017 Spring.
[Is] ISSN:1532-9488
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We describe an alternate technique to perform a replacement of the aortic hemiarch without the need for hypothermic circulatory arrest by axillary cannulation and arch vessel isolation. In 2015, 3 patients underwent hemiarch reconstructions for ascending aortic aneurysms that extended into the arch. Each was performed using right axillary cannulation, isolation and clamping of the innominate artery with isolation, and tangential clamping of the aorta distal to the innominate. There were no neurologic events and no perioperative morbidity or mortality.
[Mh] Termos MeSH primário: Aorta Torácica/cirurgia
Aneurisma da Aorta Torácica/cirurgia
Implante de Prótese Vascular/métodos
[Mh] Termos MeSH secundário: Aorta Torácica/fisiopatologia
Aneurisma da Aorta Torácica/fisiopatologia
Artéria Axilar/fisiopatologia
Artéria Axilar/cirurgia
Implante de Prótese Vascular/efeitos adversos
Tronco Braquiocefálico/fisiopatologia
Tronco Braquiocefálico/cirurgia
Ponte Cardiopulmonar
Parada Circulatória Induzida por Hipotermia Profunda
Constrição
Seres Humanos
Fluxo Sanguíneo Regional
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE


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[PMID]:28659638
[Au] Autor:Franquelim HG; Schwille P
[Ad] Endereço:Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
[Ti] Título:Revolving around constriction by ESCRT-III.
[So] Source:Nat Cell Biol;19(7):754-756, 2017 Jun 29.
[Is] ISSN:1476-4679
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The endosomal sorting complex required for transport (ESCRT)-III is critical for membrane abscission; however, the mechanism underlying ESCRT-III-mediated membrane constriction remains elusive. A study of the dynamic assembly and disassembly of the ESCRT-III machinery in vitro and in vivo now suggests that the turnover of the observed spiralling filaments is critical for membrane abscission during cytokinesis.
[Mh] Termos MeSH primário: Citocinese
Complexos Endossomais de Distribuição Requeridos para Transporte
[Mh] Termos MeSH secundário: Constrição
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Endosomal Sorting Complexes Required for Transport)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1038/ncb3569


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[PMID]:28651256
[Au] Autor:Jessee MB; Dankel SJ; Buckner SL; Mouser JG; Mattocks KT; Loenneke JP
[Ad] Endereço:Kevser Ermin Applied Physiology Laboratory, University of Mississippi, Health, Exercise Science, and Recreation Management, University, United States.
[Ti] Título:The Cardiovascular and Perceptual Response to Very Low Load Blood Flow Restricted Exercise.
[So] Source:Int J Sports Med;38(8):597-603, 2017 Jul.
[Is] ISSN:1439-3964
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:This study sought to compare cardiovascular and perceptual responses to blood flow restriction (BFR) exercise using various pressure and load combinations. Fourteen participants completed four sets of BFR elbow flexion using 10, 15 and 20% 1RM with 40 and 80% arterial occlusion pressure (AOP). AOP was measured before and after exercise. Perceived exertion (RPE) and discomfort were assessed before exercise and after each set. Data presented as mean (95% CI), except for RPE and discomfort: 25 , 50 , 75 percentiles. AOP increased post-exercise (p<0.001) with larger magnitudes seen when increasing load and pressure (p<0.001) [e. g., 10/40 ΔAOP: 21 (10, 32) mmHg vs. 20/80 ΔAOP: 62 (45, 78) mmHg], which also augmented RPE (p<0.001) [e. g., 4th set 10/40: (7, 8.5, 12) vs. 4th set 20/80: (12.75, 15.5, 17.25)] and discomfort (p<0.001) [e. g., 4 set 10/40: (0.75, 2, 4.25) vs. 4 set 20/80: (4.25, 6, 8,)]. Volume increased via greater loads (p<0.001), and participants only reached failure during 20% 1RM conditions [20/40: 74 (74, 75) repetitions; 20/80: 71 (68, 75) repetitions]. When performing BFR exercise with very low loads the magnitudes of the cardiovascular and perceptual responses are augmented by increasing the load and by applying a higher relative pressure.
[Mh] Termos MeSH primário: Pressão Sanguínea
Exercício/fisiologia
Músculo Esquelético/irrigação sanguínea
Fluxo Sanguíneo Regional/fisiologia
[Mh] Termos MeSH secundário: Adulto
Artérias/fisiologia
Constrição
Cotovelo
Feminino
Seres Humanos
Masculino
Treinamento de Resistência
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170627
[St] Status:MEDLINE
[do] DOI:10.1055/s-0043-109555


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[PMID]:28625489
[Au] Autor:Bertozzi MM; Rossaneis AC; Fattori V; Longhi-Balbinot DT; Freitas A; Cunha FQ; Alves-Filho JC; Cunha TM; Casagrande R; Verri WA
[Ad] Endereço:Department of General Pathology, Biological Sciences Center, Londrina State University, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, 86057-970 Londrina, Parana, Brazil.
[Ti] Título:Diosmin reduces chronic constriction injury-induced neuropathic pain in mice.
[So] Source:Chem Biol Interact;273:180-189, 2017 Aug 01.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Injury or dysfunction of somatosensory system induces a complex syndrome called neuropathic pain, which still needs adequate pharmacological control. The current pharmacological treatments were in part developed from natural compounds. Flavonoids are natural polyphenolic molecules presenting varied biological activities and low toxicity. The flavonoid diosmin is a safe compound with good tolerability and low toxicity. This study evaluated the antinociceptive effect of diosmin in the sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain model. Male Swiss mice were submitted to CCI and 7 days after, diosmin at 1 or 10 mg/kg was administrated intraperitoneally. Mechanical (electronic analgesimeter) and thermal (hot plate) hyperalgesia were evaluated 1-24 h after treatment. The role of the NO/cGMP/PKG/KATP channel signaling pathway in the analgesic effect of diosmin was evaluated using the pretreatment with L-NAME (an inhibitor of NOS), ODQ (an inhibitor of soluble guanylate cyclase), KT5823 (an inhibitor of PKG), or glibenclamide (an ATP-sensitive K+ channels blocker). Single treatment with diosmin inhibited in a dose-dependent manner CCI-induced mechanical and thermal hyperalgesia by activating the NO/cGMP/PKG/KATP channel signaling pathway and inhibiting spinal cord cytokine (Il-1ß and Il-33/St2) and glial cells activation (microglia - Iba-1, oligodendrocytes - Olig2) mRNA expression markers. Daily treatment during 7 days with diosmin inhibited CCI-induced mechanical and thermal hyperalgesia by inhibiting spinal cord cytokine (Il-1ß, Tnfα, and Il-33/St2) and glial cells activation (astrocytes - Gfap, Iba-1, and Olig2) markers mRNA expression. In conclusion, diosmin inhibits neuropathic spinal cord nociceptive mechanisms suggesting this flavonoid as a potential therapeutic molecule to reduce nerve lesion-induced neuropathic pain.
[Mh] Termos MeSH primário: Dor Crônica/tratamento farmacológico
Diosmina/uso terapêutico
Hiperalgesia/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Dor Crônica/metabolismo
Dor Crônica/patologia
Constrição
Diosmina/administração & dosagem
Hiperalgesia/metabolismo
Hiperalgesia/patologia
Injeções Intraperitoneais
Masculino
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7QM776WJ5N (Diosmin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE


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[PMID]:28579560
[Au] Autor:Wei J; Song J; Jiang S; Zhang G; Wheeler D; Zhang J; Wang S; Lai EY; Wang L; Buggs J; Liu R
[Ad] Endereço:Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, Florida.
[Ti] Título:Role of intratubular pressure during the ischemic phase in acute kidney injury.
[So] Source:Am J Physiol Renal Physiol;312(6):F1158-F1165, 2017 Jun 01.
[Is] ISSN:1522-1466
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acute kidney injury (AKI) induced by clamping of renal vein or pedicle is more severe than clamping of artery, but the mechanism has not been clarified. In the present study, we tested our hypothesis that increased proximal tubular pressure (P ) during the ischemic phase exacerbates kidney injury and promotes the development of AKI. We induced AKI by bilateral clamping of renal arteries, pedicles, or veins for 18 min at 37°C, respectively. P during the ischemic phase was measured with micropuncture. We found that higher P was associated with more severe AKI. To determine the role of P during the ischemic phase on the development of AKI, we adjusted the P by altering renal artery pressure. We induced AKI by bilateral clamping of renal veins, and the P was changed by adjusting the renal artery pressure during the ischemic phase by constriction of aorta and mesenteric artery. When we decreased renal artery pressure from 85 ± 5 to 65 ± 8 mmHg, P decreased from 53.3 ± 2.7 to 44.7 ± 2.0 mmHg. Plasma creatinine decreased from 2.48 ± 0.23 to 1.91 ± 0.21 mg/dl at 24 h after renal ischemia. When we raised renal artery pressure to 103 ± 7 mmHg, P increased to 67.2 ± 5.1 mmHg. Plasma creatinine elevated to 3.17 ± 0.14 mg·dl·24 h after renal ischemia. Changes in KIM-1, NGAL, and histology were in the similar pattern as plasma creatinine. In summary, we found that higher P during the ischemic phase promoted the development of AKI, while lower P protected from kidney injury. P may be a potential target for treatment of AKI.
[Mh] Termos MeSH primário: Lesão Renal Aguda/fisiopatologia
Pressão Arterial
Isquemia/fisiopatologia
Túbulos Renais/fisiopatologia
Artéria Renal/fisiopatologia
Circulação Renal
Veias Renais/fisiopatologia
[Mh] Termos MeSH secundário: Lesão Renal Aguda/metabolismo
Lesão Renal Aguda/patologia
Lesão Renal Aguda/prevenção & controle
Animais
Constrição
Creatinina/sangue
Modelos Animais de Doenças
Receptor Celular 1 do Vírus da Hepatite A/sangue
Isquemia/metabolismo
Isquemia/patologia
Isquemia/prevenção & controle
Túbulos Renais/metabolismo
Túbulos Renais/patologia
Lipocalina-2/sangue
Masculino
Camundongos Endogâmicos C57BL
Artéria Renal/cirurgia
Veias Renais/cirurgia
Índice de Gravidade de Doença
Fatores de Tempo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Havcr1 protein, mouse); 0 (Hepatitis A Virus Cellular Receptor 1); 0 (Lipocalin-2); 126469-30-5 (Lcn2 protein, mouse); AYI8EX34EU (Creatinine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1152/ajprenal.00527.2016


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[PMID]:28526223
[Au] Autor:Katheria AC; Brown MK; Faksh A; Hassen KO; Rich W; Lazarus D; Steen J; Daneshmand SS; Finer NN
[Ad] Endereço:Department of Perinatology, Neonatal Research Institute at Sharp Mary Birch Hospital for Women and Newborns, San Diego, CA. Electronic address: anup.katheria@sharp.com.
[Ti] Título:Delayed Cord Clamping in Newborns Born at Term at Risk for Resuscitation: A Feasibility Randomized Clinical Trial.
[So] Source:J Pediatr;187:313-317.e1, 2017 Aug.
[Is] ISSN:1097-6833
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Infants may benefit if resuscitation could be provided with an intact umbilical cord. Infants identified at risk for resuscitation were randomized to 1- or 5-minute cord clamping. The 5-minute group had greater cerebral oxygenation and blood pressure. Studies are needed to determine whether this translates into improved outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02827409.
[Mh] Termos MeSH primário: Parto Obstétrico/métodos
Ressuscitação/métodos
Cordão Umbilical/cirurgia
[Mh] Termos MeSH secundário: Constrição
Estudos de Viabilidade
Feminino
Seres Humanos
Recém-Nascido
Masculino
Gravidez
Risco
Nascimento a Termo
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170521
[St] Status:MEDLINE


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[PMID]:28410923
[Au] Autor:Perini P; de Troia A; Tecchio T; Azzarone M; Bianchini Massoni C; Salcuni P; Freyrie A
[Ad] Endereço:Section of Vascular Surgery, Department of Surgery, University Hospital of Parma, Parma, Italy. Electronic address: p.perini@live.com.
[Ti] Título:Infrarenal endograft clamping in late open conversions after endovascular abdominal aneurysm repair.
[So] Source:J Vasc Surg;66(4):1048-1055, 2017 Oct.
[Is] ISSN:1097-6809
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to report the technical aspects and outcomes of late open conversion (LOC) after endovascular aneurysm repair (EVAR) in a single center by using exclusively infrarenal clamping of the endograft as an alternative to suprarenal or supraceliac aortic clamping. METHODS: A retrospective analysis of EVAR requiring late explantation (>30 days) from January 1996 to October 2016 was performed. Patients' demographics, type of endograft, duration of implantation, reason for removal, extent of stent graft removal, type of reconstruction, 30-day mortality, postoperative complications, and long-term survival were obtained for analysis. RESULTS: During the study period, 28 patients required LOC. The mean age at conversion was 75.11 ± 6.65 years; 26 of 28 (92.86%) were male. Grafts were excised after a median of 41.4 months (range, 5.97-112.67 months), with 21 of 28 explantations (75%) performed electively. Multiple types of EVAR devices have been explanted; suprarenal fixation was present in 75% of the cases. The indication for LOC was the presence of an endoleak in 27 cases (20 type I, 4 type II associated with aneurysm growth, 3 type III, and 3 endotensions; in 3 cases, multiple types of endoleak were present) and graft thrombosis in 1 case. All patients underwent a transperitoneal approach with infrarenal clamping. No patient required revascularization of visceral or renal vessels. Complete removal of the stent graft was performed in 8 of 28 cases, partial removal in the remaining 20 cases (with conservation of the proximal portion in 16 of 20 cases). Technical success was 100%. Overall 30-day mortality was 7.14% (2/28). The 30-day mortality was 9.5% in elective patients and 0% in the urgent setting; this difference was not statistically significant (P = .56). Postoperative kidney injury rate was 7.7% (2/26). Mean follow-up was 47.37 ± 55.67 months (range, 0.23-175.07 months). The estimated 5-year survival rate was 78%. No aneurysm-related death or additional procedure occurred during follow-up. CONCLUSIONS: LOC after EVAR using infrarenal clamping of the endograft is a feasible and effective technique, with satisfactory postoperative mortality and morbidity. This method allows simplification of the surgical technique and may avoid renal and visceral complications related to suprarenal or supraceliac clamping.
[Mh] Termos MeSH primário: Aneurisma da Aorta Abdominal/cirurgia
Implante de Prótese Vascular/instrumentação
Prótese Vascular
Remoção de Dispositivo/métodos
Procedimentos Endovasculares/instrumentação
Complicações Pós-Operatórias/cirurgia
Stents
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Aneurisma da Aorta Abdominal/diagnóstico por imagem
Aneurisma da Aorta Abdominal/mortalidade
Aortografia/métodos
Implante de Prótese Vascular/efeitos adversos
Implante de Prótese Vascular/mortalidade
Angiografia por Tomografia Computadorizada
Constrição
Remoção de Dispositivo/efeitos adversos
Remoção de Dispositivo/mortalidade
Procedimentos Endovasculares/efeitos adversos
Procedimentos Endovasculares/mortalidade
Estudos de Viabilidade
Feminino
Seres Humanos
Itália
Masculino
Meia-Idade
Complicações Pós-Operatórias/diagnóstico por imagem
Complicações Pós-Operatórias/etiologia
Complicações Pós-Operatórias/mortalidade
Desenho de Prótese
Reoperação
Estudos Retrospectivos
Fatores de Risco
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE


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[PMID]:28404626
[Au] Autor:Quast C; Alter C; Ding Z; Borg N; Schrader J
[Ad] Endereço:From the Division of Cardiology, Pulmonary Diseases and Vascular Medicine (C.Q.) and Department of Molecular Cardiology (C.Q., C.A., Z.D., N.B., J.S.), University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Germany.
[Ti] Título:Adenosine Formed by CD73 on T Cells Inhibits Cardiac Inflammation and Fibrosis and Preserves Contractile Function in Transverse Aortic Constriction-Induced Heart Failure.
[So] Source:Circ Heart Fail;10(4), 2017 Apr.
[Is] ISSN:1941-3297
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Structural damage during heart failure development leads to increased infiltration of leukocytes. Because purinergic signaling on immune cells may impact on the inflammatory response, we evaluated the role of ecto-5'-nucleotidase (CD73) on the development of heart failure after transverse aortic constriction (TAC) using global and T-cell-specific CD73 mice. METHODS AND RESULTS: Leukocytes infiltrating the failing heart were analyzed by a multistep enzymatic procedure over a period of 16 weeks using fluorescence-activated cell sorting. TAC significantly enhanced the infiltration of leukocytes, especially T cells. The fraction of CD73 expressing cells increased over time exclusively on cytotoxic T cells, T-helper cells, and regulatory T cells. Cardiac function significantly declined in T-cell-specific CD4-Cre CD73 mice identical to that observed in global CD73 mutants and was associated with enhanced fibrosis (collagen, laminin, vimentin, periostin). Expression analysis by quantitative reverse transcription polymerase chain reaction of extracellular purine degrading enzymes and P1 and P2 receptors on T cells isolated from the injured heart revealed profound upregulation of the enzymatic machinery for hydrolysis of extracellular adenosine triphosphate and nicotinamide adenine dinucleotide, both pathways converging in the formation of AMP and adenosine via CD73. Among the P1 receptors, only the A2a receptor was significantly upregulated after TAC. T cells isolated from TAC-treated hearts show enhanced production of proinflammatory cytokines (interleukin-3, interleukin-6, interleukin-13, interleukin-17, macrophage inflammatory proteins-1α, and macrophage inflammatory proteins-1ß) when CD73 was lacking. CONCLUSIONS: Our data provide first evidence that CD73 on T cells plays an important anti-inflammatory role in TAC-induced heart failure, which is associated with antifibrotic activity and reduced production of proinflammatory cytokines most likely by activation of the adenosine A2a receptor.
[Mh] Termos MeSH primário: 5´-Nucleotidase/metabolismo
Insuficiência Cardíaca/imunologia
Inflamação/imunologia
Transdução de Sinais/imunologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: 5'-Nucleotidase/deficiência
5'-Nucleotidase/imunologia
Adenosina/imunologia
Trifosfato de Adenosina/metabolismo
Animais
Aorta/enzimologia
Colágeno/imunologia
Constrição
Modelos Animais de Doenças
Fibrose/enzimologia
Insuficiência Cardíaca/genética
Interleucina-3/metabolismo
Masculino
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-3); 8L70Q75FXE (Adenosine Triphosphate); 9007-34-5 (Collagen); EC 3.1.3.5 (5'-Nucleotidase); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170418
[Lr] Data última revisão:
170418
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170414
[St] Status:MEDLINE



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