WILLIAM SALIBE FILHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
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- Use of medical therapies before pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension patients with severe hemodynamic impairment(2020) CASTRO, Marcela Araujo; PILOTO, Bruna; FERNANDES, Caio Julio Cesar dos Santos; JARDIM, Carlos; SALIBE FILHO, William; OLEAS, Francisca Gavilanes; ALVES, Jose Leonidas; MORINAGA, Luciana Tamie Kato; HOETTE, Susana; TERRA FILHO, Mario; FREITAS FILHO, Orival; JATENE, Fabio Biscegli; SOUZA, RogerioChronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, characterized by non-resolving fibro-thrombotic obstructions of large pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for the disease, significantly improving survival. Patients with worse hemodynamic profile have worse prognosis after surgery, raising the question of whether the use of medical therapy prior to surgery to optimize hemodynamics could improve outcomes. The aim of this study was to evaluate the role of medical therapy pre-PEA, according to the hemodynamic profile at the diagnosis. We retrospectively analyzed all patients submitted to PEA, from January 2013 to December 2017. Functional, clinical and hemodynamic data were collected to evaluate the main prognostic determinants. Patients were stratified according to the hemodynamic severity and use of targeted therapies prior to surgery. A total of 108 patients were included. Thirty-five patients (32,4%) used targeted therapy pre-PEA. The use of medical therapy delayed the surgical procedure by about 7 months. There was no difference in overall survival between patients that received targeted therapy and those treated only with supportive therapy (87.8% vs 80.3%, respectively, p = 0.426). Nevertheless, when analyzing the group of patients with severe hemodynamic impairment, defined by low cardiac output(< 3.7L/min) at baseline, patients treated with targeted therapies presented a significantly better one-year survival. In higher-risk CTEPH patients, characterized by the presence of low cardiac output, the use of targeted therapies prior to PEA was associated with better outcome, suggesting a potential role for pre-operative use of medical treatment in this particular subgroup.
- Loss of response to calcium channel blockers after long-term follow up in idiopathic pulmonary arterial hypertension(2020) PILOTO, Bruna; FERNANDES, Caio; JARDIM, Carlos; CASTRO, Marcela; SALIBE-FILHO, William; ALVES-JR, Jose Leonidas; MORINAGA, Luciana; SOBRAL-ALVES, Juliana; HOETTE, Susana; TERRA-FILHO, Mario; SOUZA, Rogerio
- Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension(2020) SALIBE-FILHO, William; ARAUJO, Thais L. S.; MELO, Everton G.; COIMBRA, Luiza B. C. T.; LAPA, Monica S.; ACENCIO, Milena M. P.; FREITAS-FILHO, Orival; CAPELOZZI, Vera Luiza; TEIXEIRA, Lisete Ribeiro; FERNANDES, Caio J. C. S.; JATENE, Fabio Biscegli; LAURINDO, Francisco R. M.; TERRA-FILHO, MarioThe pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm(2)) or low- (5 dynes/cm(2)) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.
- Lung Cavities in Chronic Thromboembolic Pulmonary Hypertension(2020) FERNANDES, Caio Julio Cesar dos Santos; OLIVEIRA, Ellen Pierre de; SALIBE-FILHO, Willian; TERRA-FILHO, Mario; JARDIM, Carlos Vianna Poyares; KATO-MORINAGA, Luciana Tamie; HOETTE, Susana; SOUZA, Rogerio deOBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a unique form of pulmonary hypertension (PH) that arises from obstruction of the pulmonary vessels by recanalized thromboembolic material. CTEPH has a wide range of radiologic presentations. Commonly, it presents as main pulmonary artery enlargement, peripheral vascular obstructions, bronchial artery dilations, and mosaic attenuation patterns. Nevertheless, other uncommon presentations have been described, such as lung cavities. These lesions may be solely related to chronic lung parenchyma ischemia but may also be a consequence of concomitant chronic infectious conditions. The objective of this study was to evaluate the different etiologies that cause lung cavities in CTEPH patients. METHODS: A retrospective data analysis of the medical records of CTEPH patients in a single reference PH center that contained or mentioned lung cavities was conducted between 2013 and 2016. RESULTS: Seven CTEPH patients with lung cavities were identified. The cavities had different sizes, locations, and wall thicknesses. In two patients, the cavities were attributed to pulmonary infarction; in 5 patients, an infectious etiology was identified. CONCLUSION: Despite the possibility of being solely associated with chronic lung parenchyma ischemia, most cases of lung cavities in CTEPH patients were associated with chronic granulomatous diseases, reinforcing the need for active investigation of infectious agents in this setting.