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1.
Medicine (Baltimore) ; 99(16): e19814, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312000

RESUMO

RATIONALE: Behçet Disease (BD) is a chronic inflammatory vasculitis with thrombogenicity and multisystem involvement. Deep vein thrombosis (DVT) in the lower extremities is the most frequent manifestation of vascular involvement in BD. The causes of thrombosis vary widely and include congenital predisposition and acquired factors, but of all the thrombosis, the cause is rarely BD. Furthermore, there are few reports of treatment for thrombosis in BD. PATIENT CONCERNS: We herein describe the case of an Asian male patient aged 40 years, admitted to our hospital for left leg pain, edema, and swelling. DIAGNOSES: We confirmed the DVT and pulmonary artery thrombosis (PAT) by contrast computed tomography angiogram. At the same time, the patient developed oral ulcerations and skin lesions consistent with BD. INTERVENTIONS: The patient was initially treated with anticoagulants. However, because the improvement of DVT was inadequate, we added colchicine in anticipation of anti-inflammatory effects. After that, anticoagulation was discontinued, and only colchicine was continuously prescribed. OUTCOMES: We observed an almost complete resolution of DVT and PAT with no recurrence of thrombosis for 6 months after discharge. LESSONS: This case shows us that we should consider BD as a differential diagnosis of DVT and that colchicine therapy is effective for inflammation-induced thrombosis in BD.


Assuntos
Síndrome de Behçet/complicações , Colchicina/uso terapêutico , Moduladores de Tubulina/uso terapêutico , Trombose Venosa/tratamento farmacológico , Adulto , Anticoagulantes/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Síndrome de Behçet/patologia , Colchicina/administração & dosagem , Angiografia por Tomografia Computadorizada/métodos , Quimioterapia Combinada , Edema/diagnóstico , Edema/etiologia , Humanos , Perna (Membro)/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Dor/diagnóstico , Dor/etiologia , Artéria Pulmonar/patologia , Trombose/tratamento farmacológico , Resultado do Tratamento , Moduladores de Tubulina/administração & dosagem , Trombose Venosa/etiologia
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(3): 223-227, 2020 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-32164093

RESUMO

Objective: To investigate the efficacy and safety of transcatheter embolization for the treatment of pulmonary artery pseudoaneurysms (PAPs) with massive hemoptysis via both arterial and venous access. Methods: The clinical data of 15 patients of pulmonary tuberculosis presenting with massive hemoptysis, who were confirmed by CTA/DSA with PAPs at the Second Affiliated Hospital of Hainan Medical University from January 2016 to February 2018, were retrospectively analyzed. The imaging presentation, technical and clinical success of endovascular treatment, and recurrence of hemoptysis within 1 year was recorded. Results: A total of 15 PAPs were involved. Fourteen PAPs were confirmed by pulmonary CTA and one by angiography. Six PAPs were visualized during bronchial artery angiography, 4 PAPs during pulmonary artery angiography, and 4 PAPs both. One PAP was not shown during catheter-directed angiography. Except for one patient who died of asphyxia due to severe hemoptysis undergoing embolization, hemoptysis relapse was achieved in 14 patients after endovascular treatment. During 12 months follow-up, one patient underwent surgical resection because of recurrent hemoptysis 2 weeks after embolization, and another patient with recurrence hemoptysis 3 months after embolization received repeated intervention and hemoptysis relapsed. Conclusion: Transcatheter embolization via dual access is effective and feasible for the treatment of PAPs with massive hemoptysis in patients with pulmonary tuberculosis, but still some risks.


Assuntos
Falso Aneurisma , Embolização Terapêutica , Hemoptise , Tuberculose Pulmonar , Falso Aneurisma/complicações , Falso Aneurisma/terapia , Angiografia , Artérias Brônquicas , Hemoptise/etiologia , Hemoptise/terapia , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/complicações
3.
Crit Rev Oncol Hematol ; 147: 102889, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035299

RESUMO

Only a few hundred cases of intimal sarcomas of pulmonary artery (ISPA) were reported on the literature. Diagnosis of this rare entity is a challenging dilemma with the need for a high expertise in the radiological and pathological identification of ISPA. Treatment strategies rely initially on an early aggressive surgery aiming for complete surgical resection with clear margins while no clear recommendations guiding the choice for additional drug therapy or radiotherapy exist. In this article, we perform an extensive review of the literature on ISPA with details on the clinical presentation, diagnosis and management strategies. An additional goal of this paper is to make practicing oncologists aware of this rare entity with clear idea on the initial management.


Assuntos
Artéria Pulmonar/patologia , Sarcoma/diagnóstico , Sarcoma/cirurgia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/cirurgia , Humanos , Valva Pulmonar/patologia , Valva Pulmonar/cirurgia , Sarcoma/patologia , Neoplasias de Tecidos Moles , Neoplasias Vasculares/patologia , Neoplasias Vasculares/terapia
4.
PLoS One ; 15(2): e0226049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32053709

RESUMO

Pulmonary hypertension is a progressive lung disease with poor prognosis due to the consequent right heart ventricular failure. Pulmonary artery remodeling and dysfunction are culprits for pathologically increased pulmonary arterial pressure, but their underlying molecular mechanisms remain to be elucidated. Previous genome-wide association studies revealed a significant correlation between the genetic locus of family with sequence similarity 13, member A (FAM13A) and various lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis; however whether FAM13A is also involved in the pathogenesis of pulmonary hypertension remained unknown. Here, we identified a significant role of FAM13A in the development of pulmonary hypertension. FAM13A expression was reduced in the lungs of mice with hypoxia-induced pulmonary hypertension. We identified that FAM13A was expressed in lung vasculatures, especially in endothelial cells. Genetic loss of FAM13A exacerbated pulmonary hypertension in mice exposed to chronic hypoxia in association with deteriorated pulmonary artery remodeling. Mechanistically, FAM13A decelerated endothelial-to-mesenchymal transition potentially by inhibiting ß-catenin signaling in pulmonary artery endothelial cells. Our data revealed a protective role of FAM13A in the development of pulmonary hypertension, and therefore increasing and/or preserving FAM13A expression in pulmonary artery endothelial cells is an attractive therapeutic strategy for the treatment of pulmonary hypertension.


Assuntos
Células Endoteliais/patologia , Transição Epitelial-Mesenquimal , Proteínas Ativadoras de GTPase/metabolismo , Hipertensão Pulmonar/patologia , Artéria Pulmonar/patologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Proteínas Ativadoras de GTPase/genética , Humanos , Pulmão/irrigação sanguínea , Masculino , Camundongos , Camundongos Knockout , Artéria Pulmonar/citologia , Transdução de Sinais , Remodelação Vascular , beta Catenina/metabolismo
5.
PLoS One ; 15(2): e0229173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32078644

RESUMO

BACKGROUND: Pulmonary artery (PA) enlargement, defined as pulmonary artery to ascending aorta diameter ratio (PA:A)>1 on computed tomography (CT), is a marker of pulmonary vascular disease in chronic lung diseases. PA enlargement is prevalent in cystic fibrosis (CF), but its relationship to hemodynamics and prognostic utility in severe CF are unknown. We hypothesized that the PA:A would have utility in identifying pulmonary hypertension (PH) in severe CF and that PA enlargement would be associated with reduced transplant-free survival. METHODS: We conducted a retrospective study of adults with CF undergoing lung transplant evaluation at a single center between 2000 and 2015. CT, right heart catheterization (RHC), and clinical data were collected. The PA:A was measured from a single CT slice. We measured associations between PA:A and invasive hemodynamic parameters including PH defined as a mPAP ≥25mmHg using adjusted linear and logistic regression models. Kaplan-Meier and adjusted Cox regression models were used to measure associations between PA:A>1, RHC-defined PH, and transplant-free survival in severe CF. RESULTS: We analyzed 78 adults with CF that had CT scans available for review, including 44 that also had RHC. RHC-defined PH defined as a mPAP ≥25mmHg was present in 36% of patients with CF undergoing transplant evaluation. The PA:A correlated with mPAP (r = 0.73; 95% CI 3.87-7.80; p<0.001) and PVR (r = 0.42, p = 0.005) and the PA:A>1 was an independent predictor of PH (aOR 4.50; 95% CI 1.05-19.2; p = 0.042). PA:A>1 was independently associated with increased hazards for death or transplant (aHR 2.69; 95% CI 1.41-5.14; P = 0.003). The presence of mPAP ≥25mmHg was independently associated with decreased survival in this cohort. CONCLUSIONS: PA enlargement is associated with pulmonary hemodynamics and PH in severe CF. PA enlargement is an independent prognostic indicator of PH and decreased survival in this population.


Assuntos
Fibrose Cística/complicações , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/patologia , Artéria Pulmonar/patologia , Adulto , Estudos de Coortes , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Artéria Pulmonar/fisiopatologia
6.
Cell Prolif ; 53(2): e12742, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943454

RESUMO

OBJECTIVES: Hypoxia is an important risk factor for pulmonary arterial remodelling in pulmonary arterial hypertension (PAH), and the Janus kinase 2 (JAK2) is believed to be involved in this process. In the present report, we aimed to investigate the role of JAK2 in vascular smooth muscle cells during the course of PAH. METHODS: Smooth muscle cell (SMC)-specific Jak2 deficient mice and their littermate controls were subjected to normobaric normoxic or hypoxic (10% O2 ) challenges for 28 days to monitor the development of PAH, respectively. To further elucidate the potential mechanisms whereby JAK2 influences pulmonary vascular remodelling, a selective JAK2 inhibitor was applied to pre-treat human pulmonary arterial smooth muscle cells (HPASMCs) for 1 hour followed by 24-hour hypoxic exposure. RESULTS: Mice with hypoxia-induced PAH were characterized by the altered JAK2/STAT3 activity in pulmonary artery smooth muscle cells. Therefore, induction of Jak2 deficiency in SMCs protected mice from hypoxia-induced increase of right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodelling. Particularly, loss of Jak2 significantly attenuated chronic hypoxia-induced PASMC proliferation in the lungs. Similarly, blockade of JAK2 by its inhibitor, TG-101348, suppressed hypoxia-induced human PASMC proliferation. Upon hypoxia-induced activation, JAK2 phosphorylated signal transducer and activator of transcription 3 (STAT3), which then bound to the CCNA2 promoter to transcribe cyclin A2 expression, thereby promoting PASMC proliferation. CONCLUSIONS: Our studies support that JAK2 could be a culprit contributing to the pulmonary vascular remodelling, and therefore, it could be a viable target for prevention and treatment of PAH in clinical settings.


Assuntos
Proliferação de Células/fisiologia , Hipóxia/metabolismo , Janus Quinase 2/antagonistas & inibidores , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipóxia/patologia , Janus Quinase 2/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Inibidores de Proteínas Quinases/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Remodelação Vascular/efeitos dos fármacos , Remodelação Vascular/fisiologia
7.
Toxicol In Vitro ; 62: 104668, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629073

RESUMO

Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PASMCs induced by MA. Linear regression analysis showed that knockdown of Nrf2 promoted the positive correlation of relative ROS level with proliferation of PASMCs. Therefore, chronic exposure to MA induces pulmonary arterial remodeling by Nrf2-mediated imbalance of redox system to aggravate oxidative stress, and Nrf2 is a possible target for the treatment of MA-lung toxicity.


Assuntos
Estimulantes do Sistema Nervoso Central/toxicidade , Metanfetamina/toxicidade , Miócitos de Músculo Liso/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Masculino , Miócitos de Músculo Liso/metabolismo , Fator 2 Relacionado a NF-E2/genética , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
10.
Life Sci ; 238: 116974, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639399

RESUMO

AIM: Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility and intracellular Ca2+ transient in rats with MCT-induced PAH. MAIN METHODS: Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes. KEY FINDINGS: Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes. SIGNIFICANCE: Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.


Assuntos
Insuficiência Cardíaca/prevenção & controle , Hipertensão Pulmonar/complicações , Hipertrofia Ventricular Direita/prevenção & controle , Contração Muscular , Miócitos Cardíacos/patologia , Condicionamento Físico Animal , Artéria Pulmonar/patologia , Remodelação Ventricular , Animais , Cálcio , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/patologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/patologia , Masculino , Ratos , Ratos Wistar , Corrida
11.
Nat Commun ; 10(1): 4143, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515519

RESUMO

In pulmonary hypertension vascular remodeling leads to narrowing of distal pulmonary arterioles and increased pulmonary vascular resistance. Vascular remodeling is promoted by the survival and proliferation of pulmonary arterial vascular cells in a DNA-damaging, hostile microenvironment. Here we report that levels of Eyes Absent 3 (EYA3) are elevated in pulmonary arterial smooth muscle cells from patients with pulmonary arterial hypertension and that EYA3 tyrosine phosphatase activity promotes the survival of these cells under DNA-damaging conditions. Transgenic mice harboring an inactivating mutation in the EYA3 tyrosine phosphatase domain are significantly protected from vascular remodeling. Pharmacological inhibition of the EYA3 tyrosine phosphatase activity substantially reverses vascular remodeling in a rat model of angio-obliterative pulmonary hypertension. Together these observations establish EYA3 as a disease-modifying target whose function in the pathophysiology of pulmonary arterial hypertension can be targeted by available inhibitors.


Assuntos
Proteínas de Ligação a DNA/metabolismo , /fisiopatologia , Remodelação Vascular , Animais , Apoptose/efeitos dos fármacos , Benzobromarona/análogos & derivados , Benzobromarona/farmacologia , Cardiomegalia/complicações , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Masculino , Camundongos Transgênicos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos
12.
Int J Mol Sci ; 20(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540416

RESUMO

We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.


Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Progressão da Doença , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Masculino , Monocrotalina , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley
13.
Nat Commun ; 10(1): 3551, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391533

RESUMO

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease of cardiopulmonary units. No cure is currently available due to an incomplete understanding of vascular remodeling. Here we identify CD146-hypoxia-inducible transcription factor 1 alpha (HIF-1α) cross-regulation as a key determinant in vascular remodeling and PAH pathogenesis. CD146 is markedly upregulated in pulmonary artery smooth muscle cells (PASMCs/SMCs) and in proportion to disease severity. CD146 expression and HIF-1α transcriptional program reinforce each other to physiologically enable PASMCs to adopt a more synthetic phenotype. Disruption of CD146-HIF-1α cross-talk by genetic ablation of Cd146 in SMCs mitigates pulmonary vascular remodeling in chronic hypoxic mice. Strikingly, targeting of this axis with anti-CD146 antibodies alleviates established pulmonary hypertension (PH) and enhances cardiac function in two rodent models. This study provides mechanistic insights into hypoxic reprogramming that permits vascular remodeling, and thus provides proof of concept for anti-remodeling therapy for PAH through direct modulation of CD146-HIF-1α cross-regulation.


Assuntos
Retroalimentação Fisiológica , Hipertensão Pulmonar/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Remodelação Vascular , Animais , Antígeno CD146/genética , Antígeno CD146/metabolismo , Hipóxia Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , Camundongos , Camundongos Knockout , Monocrotalina/toxicidade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Cultura Primária de Células , Artéria Pulmonar/citologia , Artéria Pulmonar/patologia , Ratos , Índice de Gravidade de Doença , Regulação para Cima
14.
Int J Chron Obstruct Pulmon Dis ; 14: 1323-1332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417249

RESUMO

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.


Assuntos
Reação de Fase Aguda , Pulmão , Linfócitos/imunologia , Artéria Pulmonar , Doença Pulmonar Obstrutiva Crônica , Proteína Amiloide A Sérica/análise , Proteínas da Fase Aguda/análise , Proteínas da Fase Aguda/imunologia , Reação de Fase Aguda/sangue , Reação de Fase Aguda/imunologia , Correlação de Dados , Feminino , Humanos , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/imunologia , Artéria Pulmonar/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Espirometria/métodos
15.
BMC Med Imaging ; 19(1): 65, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412797

RESUMO

BACKGROUND: Computed tomography pulmonary angiography (CTPA) is the gold standard for the diagnosis of pulmonary embolism (PE). However, contrast is contraindicated in some patients. The purpose of this study was to determine the diagnostic accuracy of unenhanced multidetector CT (MDCT) for diagnosis of central PE using CTPA as the gold standard. METHODS: The records of patients with suspected PE seen between 2010 and 2013 were retrospectively reviewed. Inclusion criteria were an acute, central PE confirmed by CTPA and non-enhanced MDCT before contrast injection. Patients with a PE ruled out by CTPA served as a control group. MDCT findings studied were high-attenuation emboli in pulmonary artery (PA), main PA dilatation > 33.2 mm, and peripheral wedge-shaped consolidation. Receiver operating characteristic (ROC) analysis was used to determine the sensitivity and specificity of unenhanced MDCT to detect PE. Wells score of all patients were calculated using data extracted from medical records prior to imaging analysis. RESULTS: Thirty-two patients with a PE confirmed by CTPA and 32 with a PE ruled out by CTPA were included. Among the three main MDCT findings, high-attenuation emboli in the PA showed best diagnostic performance (Sensitivity 72.9%; Specificity 100%), followed by main PA dilatation > 33.2 mm (sensitivity 46.9%; specificity 90.6%), and peripheral wedge-shaped consolidation (sensitivity 43.8%; specificity 78.1%). Given any one or more positive findings on unenhanced MDCT, the sensitivity was 96.9% and specificity was 71.9% for a diagnosis of PE in patients. The area under the curve (AUC) of a composite measure of unenhanced MDCT findings (0.909) was significantly higher than that of the Wells score (0.688), indicating unenhanced MDCT was reliable for detecting PE than Wells score. CONCLUSIONS: Unenhanced MDCT is an alternative for the diagnosis of acute central PE when CTPA is not available.


Assuntos
Tomografia Computadorizada Multidetectores/métodos , Artéria Pulmonar/patologia , Embolia Pulmonar/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Angiografia por Tomografia Computadorizada , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
Cardiovasc Pathol ; 43: 107143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437715

RESUMO

We report an autopsy-proven case of a 33-year-old man who died of intimal sarcoma of the pulmonary artery. A large mass (5×4 cm) occluded the main and bilateral pulmonary arteries. Tumor cell morphology was consistent with that of undifferentiated pleomorphic sarcoma. Comprehensive histological observation of 18 pulmonary arteries from proximal to distal revealed continuous extension of the tumor from the main to the subsegmental arteries along the intima, forming an arteriosclerosis-like intimal thickening. Distal small arteries were also affected by eccentric intimal thickening or recanalization. Lung parenchyma was not involved, although there were two wedge-shaped small pulmonary infarctions caused by tumorous obstruction of the associated arteries. Histological results indicated that the intimal sarcoma in the pulmonary artery, which appeared occlusive with growth limited to the proximal artery, had in fact already spread more peripherally than expected. Both the proximal lesions and the distal small arteries were affected by peripheral tumor emboli or by pulmonary hypertension induced by the proximal tumor. However, as seen in this case, most of the occlusive tumor was located locally and intraluminally, in the proximal artery, and removing the proximal tumor by pulmonary endarterectomy was considered effective for symptomatic improvement.


Assuntos
Artéria Pulmonar/patologia , Sarcoma/patologia , Túnica Íntima/patologia , Neoplasias Vasculares/patologia , Adulto , Autopsia , Biomarcadores Tumorais/análise , Causas de Morte , Evolução Fatal , Humanos , Masculino , Artéria Pulmonar/química , Sarcoma/química , Túnica Íntima/química , Neoplasias Vasculares/química
17.
Life Sci ; 235: 116794, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31465731

RESUMO

Amongst the various forms of lung injury; pulmonary fibrosis remains the most intricate form with limited therapeutic options to both the patient and the physicians. Bleomycin (BLM) is a chemotherapeutic agent used for the treatment of various carcinomas; however, its therapeutic value is significantly limited by its associated pulmonary fibrosis. The current study highlights the prominent antioxidant, anti-inflammatory and anti-fibrotic effect of crocin against BLM-induced pulmonary fibrosis. Intratracheal BLM instillation induced significant biochemical, structural, functional and vascular pulmonary injury. BLM instillation increased oxidant load with quenching of antioxidant defenses together with increase inflammatory and fibrotic cytokines expression. Crocin significantly attenuated BLM-induced lung injury and its effect was comparable to the standard anti-fibrotic; halofuginone. The observed anti-inflammatory and anti-fibrotic and antioxidant impacts are thought to be embroiled in the therapeutic impacts of crocin. Down-regulation of TLR4, IL-10 expression is the major pathway involved in the observed anti-inflammatory effects and finally, down-regulation of tissue expression of TNF-α and TGF-ß1 is the major pathways implicated in the observed anti-fibrotic activities and modulation of Nrf2 and HO-1 pathways is the main mechanism involved in the observed antioxidant effects.


Assuntos
Bleomicina/toxicidade , Carotenoides/farmacologia , Pneumonia/prevenção & controle , Artéria Pulmonar/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Doenças Vasculares/prevenção & controle , Animais , Antibióticos Antineoplásicos , Masculino , Pneumonia/induzido quimicamente , Pneumonia/patologia , Artéria Pulmonar/patologia , Fibrose Pulmonar/complicações , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Doenças Vasculares/induzido quimicamente , Doenças Vasculares/patologia
18.
J Vet Med Sci ; 81(9): 1259-1265, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31292347

RESUMO

A 12-year-old neutered female American cocker spaniel weighing 9.9 kg was presented for evaluation with a 2-day history of dyspnea and anorexia. Echocardiography revealed severe pulmonary hypertension (estimated systolic pulmonary arterial pressure, 93.4 mmHg) with right heart enlargement, pulmonary arterial dilation, and right ventricular dysfunction. The dilation of left heart and congenital cardiac shunt were not observed. Pulmonary thromboembolism (PTE) was confirmed by computed tomographic angiography. After treatment with antiplatelet and anticoagulant, the clinical sign and the echocardiographic abnormality of right heart were improved. These echocardiographic findings are not specific for PTE, but it can be useful as a rule-in test for PTE when other causes of pulmonary hypertension are excluded and a monitor of therapeutic efficacy.


Assuntos
Doenças do Cão/diagnóstico por imagem , Hipertensão Pulmonar/veterinária , Embolia Pulmonar/veterinária , Disfunção Ventricular Direita/veterinária , Animais , Anticoagulantes/uso terapêutico , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/veterinária , Angiografia por Tomografia Computadorizada/veterinária , Doenças do Cão/etiologia , Cães , Ecocardiografia/veterinária , Feminino , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Artéria Pulmonar/patologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Disfunção Ventricular Direita/etiologia
19.
Acta Pharmacol Sin ; 40(10): 1322-1333, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31316183

RESUMO

Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKß separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/ß, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 µM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.


Assuntos
Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Administração Oral , Animais , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Biologia Computacional , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/farmacologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Masculino , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Cicatrização/efeitos dos fármacos
20.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 209-214, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257800

RESUMO

OBJECTIVE: To investigate the effects of apple polyphenols on pulmonary vascular remodeling in rats with pulmonary arterial hypertension and its mechanism. METHODS: Rats were randomly divided into 4 groups:control (Con) group, monocrotaline (MCT) group, apple polyphenol (APP) group,monocrotaline + apple polyphenol (MCT+APP) group. In Con group, rats received a subcutaneous injection of physical saline. In APP group, rats received intraperitoneal injection of 20 mg/kg APP, every other day. In MCT group, rats received a single subcutaneous injection of MCT(60 mg/kg). In MCT+APP group, rats received subcutaneous injection of 60 mg/kg MCT followed by an intraperitoneal injection of 20 mg/kg APP every other day. All the disposal lasted 3 weeks. Then the PAH-relevant indicators, such as mean pulmonary artery pressure(mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index (RVHI) ,wall thickness (WT%) and wall area (WA%) were tested. After that, the inflammatory pathway related indicators, such as interleukin1(IL-1),interleukin1(IL-6), tumor necrosis factor α(TNF-α), cyclooxygenase 2(COX-2) and myeloperoxidase(MPO) in pulmonary tissue and free intracellular Ca2+ in pulmonary smooth muscle cell(PASMC), content of eNOS and NO in endothelial cells were determined. RESULTS: Compared with the control group, the levels of mPAP, PVR, RVHI, WA%, WT%, and IL-1, IL-6, TNF-α, COX-2, MPO in tissue and the expression of Ca2 + in PASMC of MCT group were increased significantly, while the contents of eNOS and NO in endothelial cells were decreased significantly (P<0.05). Compared with the MCT group, the apple polyphenol treatment could improve the above mentioned situation, and the COX-2 and Ca2+ indicators of the apple polyphenol treatment group were decreased significantly (P<0.05). CONCLUSION: MCT can increase COX-2 expression and intracellular Ca2+ in pulmonary artery smooth muscle cells, decrease the contents of eNOS and NO in endothelial cells, while apple polyphenols can significantly inhibit these effects.


Assuntos
Malus/química , Polifenóis/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Animais , Cálcio/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Monocrotalina , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Artéria Pulmonar/patologia , Distribuição Aleatória , Ratos
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