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1.
Diagnostics (Basel) ; 14(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39001230

RESUMO

Lung transplantation (LT) constitutes the last therapeutic option for selected patients with end-stage respiratory disease. Primary graft dysfunction (PGD) is a form of severe lung injury, occurring in the first 72 h following LT and constitutes the most common cause of early death after LT. The presence of pulmonary hypertension (PH) has been reported to favor PGD development, with a negative impact on patients' outcomes while complicating medical management. Although several studies have suggested a potential association between pre-LT left ventricular diastolic dysfunction (LVDD) and PGD occurrence, the underlying mechanisms of such an association remain elusive. Importantly, the heterogeneity of the study protocols and the various inclusion criteria used to define the diastolic dysfunction in those patients prevents solid conclusions from being drawn. In this review, we aim at summarizing PGD mechanisms, risk factors, and diagnostic criteria, with a further focus on the interplay between LVDD and PGD development. Finally, we explore the predictive value of several diastolic dysfunction diagnostic parameters to predict PGD occurrence and severity.

2.
Diagnostics (Basel) ; 14(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732361

RESUMO

This comprehensive review explores the intricate aspects of left ventricular thrombus (LVT), a potential complication in both ischemic and non-ischemic cardiomyopathies. It provides a thorough understanding of left ventricular thrombus, revealing its uncommon incidence in the general population (7 cases per 10,000 patients), predominantly linked to ischemic heart diseases (ICMs) at an 80% prevalence rate. Diagnostic tools, notably transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR), demonstrate varying sensitivity but remain indispensable in specific clinical contexts related to LVT as non-invasive diagnostic modalities. A detailed comparison between ICM patients and those with non-ischemic cardiomyopathy (NICM) who have left ventricular thrombus reveals subtle distinctions with significant clinical implications. This analysis underscores the importance of these imaging techniques in distinguishing between the two conditions. Additionally, we explored the occurrence of LVT in specific non-ischemic cardiomyopathies, including Takotsubo syndrome, hypertrophic cardiomyopathy, eosinophilic myocarditis, Chagas disease, cardiac amyloidosis, and several other conditions. The article further delves into anticoagulation strategies, thoroughly examining their impact on LVT regression and patient outcomes. Pharmacological interventions, with a focus on direct oral anticoagulants, emerge as promising alternatives; however, there is insufficient information on their efficiency and safety, especially in NICM population. In conclusion, this review highlights the complex nature of LVT, incorporating a range of etiopathogenic factors, diagnostic complexities, and evolving therapeutic approaches. It emphasizes the pressing need for ongoing research in this field.

4.
Diagnostics (Basel) ; 13(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37958264

RESUMO

At the beginning of 2020, coronavirus disease 2019 (COVID-19) emerged as a new pandemic, leading to a worldwide health crisis and overwhelming healthcare systems due to high numbers of hospital admissions, insufficient resources, and a lack of standardized therapeutic protocols. Multiple genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected since its first public declaration in 2020, some of them being considered variants of concern (VOCs) corresponding to several pandemic waves. Nevertheless, a growing number of COVID-19 patients are continuously discharged from hospitals, remaining symptomatic even months after their first episode of COVID-19 infection. Long COVID-19 or 'post-acute COVID-19 syndrome' emerged as the new pandemic, being characterized by a high variability of clinical manifestations ranging from cardiorespiratory and neurological symptoms such as chest pain, exertional dyspnoea or cognitive disturbance to psychological disturbances, e.g., depression, anxiety or sleep disturbance with a crucial impact on patients' quality of life. Moreover, Long COVID is viewed as a new cardiovascular risk factor capable of modifying the trajectory of current and future cardiovascular diseases, altering the patients' prognosis. Therefore, in this review we address the current definitions of Long COVID and its pathophysiology, with a focus on cardiovascular manifestations. Furthermore, we aim to review the mechanisms of acute and chronic cardiac injury and the variety of cardiovascular sequelae observed in recovered COVID-19 patients, in addition to the potential role of Long COVID clinics in the medical management of this new condition. We will further address the role of future research for a better understanding of the actual impact of Long COVID and future therapeutic directions.

5.
Respir Med Case Rep ; 46: 101946, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025246

RESUMO

Background: Lung toxicity of angiotensin receptor blockers (sartans) have very seldom been reported in the literature despite their wide use. We here report a case of interstitial lung disease elicited by sartans, with two episodes induced by two different sartans at 10 years of interval. Case presentation: In 2012, eprosartan was the very likely cause of a drug induced interstitial lung disease in a 60 year old man. Indeed, his symptoms, consisting in a MMRC2 dyspnea and recurrent hemoptysis, completely disappeared after the removal of this drug. When the circumstances rendered it necessary to start another angiotensin receptor blocker (namely valsartan) ten years later we did not expect the same reaction to occur given among other things a very poor literature on the topic. After a few months with this medication, he however developed similar symptoms and a Chest CT imaging that was comparable to what he had in 2012.This time also the clinical picture resolved completely when the sartan was stopped. Conclusion: We report this first case of a drug induced interstitial lung disease induced by two different angiotensin receptor blockers (sartans) with a new drug challenge ten years after the first one.

6.
BMC Health Serv Res ; 23(1): 659, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340416

RESUMO

BACKGROUND: Although there are already success stories, population health management in Belgium is still in its infancy. A health system transformation approach such as population health management may be suited to address the public health issue of atherosclerotic cardiovascular disease, as this is one of the main causes of mortality in Belgium. This article aims to raise awareness about population health management in Belgium by: (a) eliciting barriers and recommendations for its implementation as perceived by local stakeholders; (b) developing a population health management approach to secondary prevention of atherosclerotic cardiovascular disease; and (c) providing a roadmap to introduce population health management in Belgium. METHODS: Two virtual focus group discussions were organized with 11 high-level decision makers in medicine, policy and science between October and December 2021. A semi-structured guide based on a literature review was used to anchor discussions. These qualitative data were studied by means of an inductive thematic analysis. RESULTS: Seven inter-related barriers and recommendations towards the development of population health management in Belgium were identified. These related to responsibilities of different layers of government, shared responsibility for the health of the population, a learning health system, payment models, data and knowledge infrastructure, collaborative relationships and community involvement. The introduction of a population health management approach to secondary prevention of atherosclerotic cardiovascular disease may act as a proof-of-concept with a view to roll out population health management in Belgium. CONCLUSIONS: There is a need to instill a sense of urgency among all stakeholders to develop a joint population-oriented vision in Belgium. This call-to-action requires the support and active involvement of all Belgian stakeholders, both at the national and regional level.


Assuntos
Doenças Cardiovasculares , Gestão da Saúde da População , Humanos , Bélgica , Doenças Cardiovasculares/prevenção & controle , Grupos Focais , Governo
7.
Cardiovasc Revasc Med ; 43: 28-35, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35641364

RESUMO

Magmaris® (Biotronik AG, Switzerland) is the first RMS and early experience has shown promising results in stable coronary artery disease. Acute coronary syndromes have been hypothesized as a potential target group for bioresorbable scaffolds, but the efficacy and safety of RMS has not been extensively studied in ST-segment elevation myocardial infarction (STEMI). BEST-MAG is a prospective multicenter trial designed to evaluate optical coherence tomography (OCT-)guided implantation of resorbable magnesium scaffold (RMS) in STEMI. Consecutive STEMI patients fulfilling inclusion/exclusion criteria were treated with RMS following a standardized OCT-based implantation technique including systematic pre- and post-dilatation, and baseline plus final OCT imaging. The primary endpoint was a device oriented composite endpoint (DOCE) including cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR) within 12 months. Clinical outcomes were compared after propensity score matching (PSM) to the results of the randomized controlled BIOSTEMI trial comparing biodegradable polymer sirolimus eluting (BP-SES) and durable polymer everolimus eluting stents (DP-EES) in STEMI. Between 15th February 2019 and 25th May 2020, 30 patients were included in 5 centers. Procedural success was achieved in all cases based on OCT control with final scaffold expansion of 82 ± 11%. At twelve-months, DOCE rate was 13.3% (n = 4), including 4 cases of TLR (13.3%) and one case of TV-MI (3.3%). No cardiac death occurred, and no scaffold thrombosis (ScT) was observed. Using PSM, DOCE rates in BP-SES and DP-EES groups were 10% and 6% respectively and TLR rates were 3.3% and 0.0%. In this study, OCT-guided RMS implantation in selected STEMI patients appeared feasible but was associated with numerically higher rates of TLR as compared with conventional drug-eluting stents, although the limited number of patients included in this analysis does not allow drawing statistically significant conclusions.


Assuntos
Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Implantes Absorvíveis , Everolimo , Humanos , Magnésio , Polímeros , Pontuação de Propensão , Estudos Prospectivos , Desenho de Prótese , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Sirolimo , Resultado do Tratamento
8.
Atherosclerosis ; 277: 369-376, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30270073

RESUMO

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD. METHODS: A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care. RESULTS: A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities. CONCLUSIONS: We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives.


Assuntos
Doenças Cardiovasculares/terapia , LDL-Colesterol/sangue , Unidades de Cuidados Coronarianos/normas , Procedimentos Clínicos/normas , Técnicas de Apoio para a Decisão , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Algoritmos , Bélgica/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Tomada de Decisão Clínica , Consenso , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Mutação , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Fluxo de Trabalho
10.
Circ Cardiovasc Imaging ; 10(5)2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28487317

RESUMO

BACKGROUND: Inflammation and intraplaque neovascularization are acknowledged to be 2 features of plaque vulnerability, although their temporal expression and their respective value in predicting clinical events are poorly understood. To determine their respective temporal associations, we conducted a comprehensive assessment of inflammation and intraplaque neovascularization in the carotid plaque of symptomatic and asymptomatic patients. METHODS AND RESULTS: Thirty patients with severe carotid stenosis underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. Plaque 18F-fluorodeoxyglucose-uptake, indicative of inflammation, was measured by calculating the target:background ratio. The presence of intraplaque neovascularization during contrast-enhanced ultrasound was judged semiquantitatively; low-grade contrast enhancement (CE) suggested its absence, and high-grade CE, the presence of neovascularization. Carotid surgery was performed 1.6±1.8 days after completing both imaging modalities in all patients, and the presence of macrophages and neovessels was quantified by immunohistochemistry. We identified a significant correlation between the target:background ratio and macrophage quantification (R=0.78; P<0.001). The number of vessels was also significantly higher in carotid plaque with high-CE (P<0.001). Surprisingly, immunohistochemistry showed that high-CE and vessel number were neither associated with an elevated target:background ratio (P=0.28 and P=0.60, respectively) nor macrophage infiltration (P=0.59 and P=0.40, respectively). Finally, macrophage infiltration and target:background ratio were higher in the carotid plaque of symptomatic patients (P=0.021 and P=0.05, respectively), whereas CE grade and the presence of neovessels were not. CONCLUSIONS: Inflammation and intraplaque neovascularization are not systematically associated in carotid plaques, suggesting a temporal separation between the 2 processes. Inflammation seems more pronounced when symptoms are present. These data highlight the challenges that face any imaging strategy designed to assess plaque vulnerability.


Assuntos
Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Inflamação/fisiopatologia , Neovascularização Patológica/fisiopatologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/fisiopatologia , Idoso , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Meios de Contraste , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Compostos Radiofarmacêuticos , Ultrassonografia
11.
Ann Thorac Surg ; 101(6): 2176-84, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26912306

RESUMO

BACKGROUND: Limited data are available regarding the prognostic value of right ventricular (RV) systolic dysfunction (RVSD) in patients with coronary artery disease. Our objective was to evaluate the effect of RVSD assessed by cardiac magnetic resonance on survival of patients with low left ventricular (LV) ejection fraction (EF) undergoing coronary bypass grafting (CABG). METHODS: We prospectively assessed overall and cardiovascular death of 107 consecutive patients (94 men; age, 66 ± 10 years) undergoing CABG who had a LVEF of 0.35 or less by cardiac magnetic resonance before CABG. RESULTS: Mean LVEF was 0.25 ± 0.07, and mean RVEF was 0.46 ± 0.16. RVSD, defined by RVEF of 0.35 or less, was present in 32 patients (30%). In-hospital mortality rate (n = 8) was significantly higher in patients with RVSD (18.7% vs 2.7%, p = 0.004). Over a median follow-up of 4.7 years, 44 patients died, 33 of a cardiovascular cause. The primary end point of cardiovascular death was reached by 15 of 32 patients with RVSD and 18 of 75 patients without RVSD (47% vs 24%, p = 0.019). Univariate survival analysis showed that age, New York Heart Association Functional Classification, diabetes, estimated glomerular filtration rate, LVEF, LV indexed end-diastolic volume, RVEF, RV indexed end-diastolic volume, RV systolic function, and The Society of Thoracic Surgeons risk score were independent predictors of the primary end point of cardiovascular death. By multivariable analysis, the Society of Thoracic Surgeons risk score (hazard ratio, 1.32; 95% confidence interval, 1.13 to 1.55; p = 0.001) and RVSD (hazard ratio, 2.14; 95% confidence interval, 1.06 to 4.31; p = 0.034) remained significant independent predictors of cardiovascular death. CONCLUSIONS: RVSD strongly and independently predicts cardiovascular death in patients with coronary artery disease and low EF undergoing CABG. Evaluation of RV function should thus be part of preoperative evaluation of such patients.


Assuntos
Ponte de Artéria Coronária/mortalidade , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Mortalidade Hospitalar , Imagem Cinética por Ressonância Magnética/métodos , Disfunção Ventricular Direita/mortalidade , Fatores Etários , Idoso , Estudos de Coortes , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Volume Sistólico/fisiologia , Análise de Sobrevida , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
13.
Clin Nucl Med ; 40(5): 448-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25549346

RESUMO

A 21-year-old patient with a D-transposition of the great arteries and a single coronary ostium underwent an atrial switch operation as newborn (Senning correction at 6 days of life in 1992). For an unrelated oncological evaluation, she underwent a recent F-FDG PET/CT. The myocardial uptake was clearly more intense in the morphological right ventricle, as this ventricle has become the systemic ventricle. On the contrary, the morphological left ventricle showed a very faint FDG uptake. This case illustrates the physiological changes related to a previous cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fluordesoxiglucose F18 , Ventrículos do Coração/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Reações Falso-Positivas , Feminino , Ventrículos do Coração/cirurgia , Humanos , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
J Nucl Med ; 55(10): 1629-35, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25082852

RESUMO

UNLABELLED: (18)F-FDG PET/CT can be used to detect arterial atherosclerotic plaque inflammation. However, avid myocardial glucose uptake may preclude its use for visualizing coronary plaques. Fatty acid loading or calcium channel blockers could decrease myocardial (18)F-FDG uptake, thus assisting coronary plaque inflammation identification. The present prospective randomized trial compared the efficacies of different interventions for suppressing myocardial (18)F-FDG uptake. We also investigated whether circulating free fatty acid (cFFA) levels predicted the magnitude of myocardial (18)F-FDG uptake. METHODS: Thirty-six volunteers ate a high-fat low-carbohydrate meal, followed by a 12-h fasting period. They were then randomized to 1 of 4 intervention groups. Group 1 received no additional preparation and served as a reference. Groups 2 and 3, respectively, received a commercial high-fat solution containing 43.8 g of lipids or 50 mL of olive oil 1 h before (18)F-FDG injection to evaluate the impact of fatty acid loading on myocardial (18)F-FDG uptake. Group 4 received verapamil to evaluate the effect of calcium channel blockers. Cardiac PET/CT was performed after administration of 370 MBq of (18)F-FDG. Myocardial uptake suppression was assessed using a qualitative visual scale and by measuring the myocardial maximum standardized uptake value (SUV(max)). Insulin, glucose, and cFFA were serially measured. RESULTS: The qualitative visual scale showed good myocardial (18)F-FDG uptake suppression in 8 of 9, 5 of 9, 4 of 9, and 8 of 9 subjects of groups 1, 2, 3, and 4, respectively (P = 0.09). SUV(max) did not significantly differ between groups (P = 0.17). Interestingly, cFFA levels were higher in volunteers with good suppression (0.80 ± 0.31 mmol/L) than in those with poor suppression (0.53 ± 0.15 mmol/L; P = 0.011). We found an inverse correlation between cFFA level (measured at (18)F-FDG injection) and the SUV(max) (R = 0.61). Receiver-operating-characteristic curve analysis identified 0.65 mmol/L cFFA as the best cutoff value to predict adequate (18)F-FDG uptake suppression (positive predictive value, 89%). CONCLUSION: A high-fat low-carbohydrate meal followed by a 12-h fasting period effectively suppressed myocardial (18)F-FDG uptake in most subjects. Neither complementary fatty acid loading nor verapamil administered 1 h before (18)F-FDG injection conferred any additional benefit. Myocardial (18)F-FDG uptake was inversely correlated with cFFA level, representing an interesting way to predict myocardial (18)F-FDG uptake suppression.


Assuntos
Vasos Coronários/patologia , Fluordesoxiglucose F18/farmacocinética , Placa Aterosclerótica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Dieta , Ácidos Graxos não Esterificados/sangue , Feminino , Voluntários Saudáveis , Humanos , Inflamação , Lipídeos/administração & dosagem , Masculino , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Óleos de Plantas/química , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Verapamil/administração & dosagem
16.
Acta Cardiol ; 68(2): 139-43, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23705555

RESUMO

BACKGROUND: The number of fitness centres has increased in Western countries, some proposing specific training programmes (cardiac patients, weight loss or seniors).There is a real risk of cardiovascular events for individuals without cardiovascular evaluation. Fitness centres could represent a place at particularly high risk for sudden cardiac arrest (SCA). OBJECTIVE AND METHODS: In this observational study, we evaluated the number of fitness centres with automatic external defibrillators (AEDs) throughout the French-speaking part of Belgium, their geographic localization, the number of attendees, and the number of SCA reported. Details of AED and SCA were obtained by telephone survey. RESUITS: A total of 51 centres were surveyed. Only 5 (9.8%) had an AED and 68.8% (35/51) of centres had > 1 staff members specifically trained in CPR. Since the opening of these facilities, 5 SCA were reported from 3 centres (5.9%). Only 2 fitness centres had an AED present at the time of the SCA.Two SCA were unwitnessed, and for another 2 victims AED was used without success. Well-conducted CPR (no AED available) resulted in the only survivor of SCA. CONCLUSION: The rate of SCA in fitness centres in French-speaking Belgium is comparable to that reported in other countries. AED were available in less than 10% of centres and no CPR trained staff was available in almost one third of the centres.


Assuntos
Desfibriladores/estatística & dados numéricos , Academias de Ginástica/estatística & dados numéricos , Arritmias Cardíacas/prevenção & controle , Bélgica , Morte Súbita Cardíaca/prevenção & controle , Humanos , Estudos Retrospectivos
17.
Biochim Biophys Acta ; 1773(4): 521-35, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17320990

RESUMO

Peroxins 5 and 7 are receptors for protein import into the peroxisomal matrix. We studied the involvement of these peroxins in the biogenesis of glycosomes in the protozoan parasite Trypanosoma brucei. Glycosomes are peroxisome-like organelles in which a major part of the glycolytic pathway is sequestered. We here report the characterization of the T. brucei homologue of PEX7 and provide several data strongly suggesting that it can bind to PEX5. Depletion of PEX5 or PEX7 by RNA interference had a severe effect on the growth of both the bloodstream-form of the parasite, that relies entirely on glycolysis for its ATP supply, and the procyclic form representative of the parasite living in the tsetse-fly midgut and in which also other metabolic pathways play a prominent role. The role of the two receptors in import of glycosomal matrix proteins with different types of peroxisome/glycosome-targeting signals (PTS) was analyzed by immunofluorescence and subcellular fractionation studies. Knocking down the expression of either receptor gene resulted, in procyclic cells, in the mislocalization of proteins with both a type 1 or 2 targeting motif (PTS1, PTS2) located at the C- and N-termini, respectively, and proteins with a sequence-internal signal (I-PTS) to the cytosol. Electron microscopy confirmed the apparent integrity of glycosomes in these procyclic cells. In bloodstream-form trypanosomes, PEX7 depletion seemed to affect only the subcellular distribution of PTS2-proteins. Western blot analysis suggested that, in both life-cycle stages of the trypanosome, the levels of both receptors are controlled in a coordinated fashion, by a mechanism that remains to be determined. The observation that both PEX5 and PEX7 are essential for the viability of the parasite indicates that the respective branches of the glycosome-import pathway in which each receptor acts might be interesting drug targets.


Assuntos
Microcorpos/metabolismo , Proteínas de Protozoários/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Trypanosoma brucei brucei/metabolismo , Sequência de Aminoácidos , Animais , Sítios de Ligação , Clonagem Molecular , Estágios do Ciclo de Vida , Microcorpos/ultraestrutura , Dados de Sequência Molecular , Receptor 2 de Sinal de Orientação para Peroxissomos , Receptor 1 de Sinal de Orientação para Peroxissomos , Ligação Proteica , Transporte Proteico , Interferência de RNA , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/deficiência , Receptores Citoplasmáticos e Nucleares/isolamento & purificação , Análise de Sequência de Proteína , Homologia de Sequência , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/ultraestrutura
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