LUIZ FELIPE PINHO MOREIRA

(Fonte: Lattes)
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Lattes
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Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • conferenceObject
    FEMALE RATS PRESENT HIGHER LUNG INFLAMMATION AFTER BRAIN DEATH FOLLOWED BY EX VIVO PERFUSION
    (2021) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG- JR., Roberto; OTTENS, Petra; ZANDEN, Judith van; VIDAL-DOS-SANTOS, Marina; MOREIRA, Luiz Felipe Pinho; ERASMUS, Michiel; LEUVENINK, Henri; BREITHAUPT-FALOPPA, Ana Cristina
  • article 33 Citação(ões) na Scopus
    Molecular and Biomechanical Clues From Cardiac Tissue Decellularized Extracellular Matrix Drive Stromal Cell Plasticity
    (2020) LIGUORI, Gabriel Romero; LIGUORI, Tacia Tavares Aquinas; MORAES, Sergio Rodrigues de; SINKUNAS, Viktor; TERLIZZI, Vincenzo; DONGEN, Joris A. van; SHARMA, Prashant K.; MOREIRA, Luiz Felipe Pinho; HARMSEN, Martin Conrad
    Decellularized-organ-derived extracellular matrix (dECM) has been used for many years in tissue engineering and regenerative medicine. The manufacturing of hydrogels from dECM allows to make use of the pro-regenerative properties of the ECM and, simultaneously, to shape the material in any necessary way. The objective of the present project was to investigate differences between cardiovascular tissues (left ventricle, mitral valve, and aorta) with respect to generating dECM hydrogels and their interaction with cells in 2D and 3D. The left ventricle, mitral valve, and aorta of porcine hearts were decellularized using a series of detergent treatments (SDS, Triton-X 100 and deoxycholate). Mass spectrometry-based proteomics yielded the ECM proteins composition of the dECM. The dECM was digested with pepsin and resuspended in PBS (pH 7.4). Upon warming to 37 degrees C, the suspension turns into a gel. Hydrogel stiffness was determined for samples with a dECM concentration of 20 mg/mL. Adipose tissue-derived stromal cells (ASC) and a combination of ASC with human pulmonary microvascular endothelial cells (HPMVEC) were cultured, respectively, on and in hydrogels to analyze cellular plasticity in 2D and vascular network formation in 3D. Differentiation of ASC was induced with 10 ng/mL of TGF-beta 1 and SM22 alpha used as differentiation marker. 3D vascular network formation was evaluated with confocal microscopy after immunofluorescent staining of PECAM-1. In dECM, the most abundant protein was collagen VI for the left ventricle and mitral valve and elastin for the aorta. The stiffness of the hydrogel derived from the aorta (6,998 +/- 895 Pa) was significantly higher than those derived from the left ventricle (3,384 +/- 698 Pa) and the mitral valve (3,233 +/- 323 Pa) (One-way ANOVA,p= 0.0008). Aorta-derived dECM hydrogel drove non-induced (without TGF-beta 1) differentiation, while hydrogels derived from the left ventricle and mitral valve inhibited TGF-beta 1-induced differentiation. All hydrogels supported vascular network formation within 7 days of culture, but ventricular dECM hydrogel demonstrated more robust vascular networks, with thicker and longer vascular structures. All the three main cardiovascular tissues, myocardium, valves, and large arteries, could be used to fabricate hydrogels from dECM, and these showed an origin-dependent influence on ASC differentiation and vascular network formation.
  • article 3 Citação(ões) na Scopus
    Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats
    (2021) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG-JR, Roberto; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano de Jesus; SILVA, Raphael dos Santos Coutinho e; ANUNCIACAO, Lucas Ferreira da; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri Gerrit Derk; BREITHAUPT-FALOPPA, Ana Cristina
    OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17 beta-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17 beta-estradiol (50 mu g/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17 beta-estradiol (50 mu g/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-alpha, IL-1 beta, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-alpha and IL-1 beta gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.
  • article 11 Citação(ões) na Scopus
    Adipose tissue-derived stromal cells' conditioned medium modulates endothelial-mesenchymal transition induced by IL-1 beta/TGF-beta 2 but does not restore endothelial function
    (2019) LIGUORI, Tacia Tavares Aquinas; LIGUORI, Gabriel Romero; MOREIRA, Luiz Felipe Pinho; HARMSEN, Martin Conrad
    Objectives Endothelial cells undergo TGF-beta-driven endothelial-mesenchymal transition (EndMT), representing up to 25% of cardiac myofibroblasts in ischaemic hearts. Previous research showed that conditioned medium of adipose tissue-derived stromal cells (ASC-CMed) blocks the activation of fibroblasts into fibrotic myofibroblasts. We tested the hypothesis that ASC-CMed abrogates EndMT and prevents the formation of adverse myofibroblasts. Materials and methods Human umbilical vein endothelial cells (HUVEC) were treated with IL-1 beta and TGF-beta 2 to induce EndMT, and the influence of ASC-CMed was assessed. As controls, non-treated HUVEC or HUVEC treated only with IL-1 beta in the absence or presence of ASC-CMed were used. Gene expression of inflammatory, endothelial, mesenchymal and extracellular matrix markers, transcription factors and cell receptors was analysed by RT-qPCR. The protein expression of endothelial and mesenchymal markers was evaluated by immunofluorescence microscopy and immunoblotting. Endothelial cell function was measured by sprouting assay. Results IL-1 beta/TGF-beta 2 treatment induced EndMT, as evidenced by the change in HUVEC morphology and an increase in mesenchymal markers. ASC-CMed blocked the EndMT-related fibrotic processes, as observed by reduced expression of mesenchymal markers TAGLN (P = 0.0008) and CNN1 (P = 0.0573), as well as SM22 alpha (P = 0.0501). The angiogenesis potential was impaired in HUVEC undergoing EndMT and could not be restored by ASC-CMed. Conclusions We demonstrated that ASC-CMed reduces IL-1 beta/TGF-beta 2-induced EndMT as observed by the loss of mesenchymal markers. The present study supports the anti-fibrotic effects of ASC-CMed through the modulation of the EndMT process.
  • conferenceObject
    SEX-DIFFERENCES ON PLATELET AGGREGATION AND MICROVASCULAR PERFUSION AFTER BRAIN DEATH IN RATS
    (2019) CORREIA, Cristiano de Jesus; BREITHAUPT-FALOPPA, Ana Cristina; SILVA, Raphael dos Santos Coutinho e; SANTOS, Marina Vidal dos; ANUNCIACAO, Lucas Ferreira da; LEUVENINK, Hendrik Gerrit Derk; MOREIRA, Luiz Felipe Pinho
  • article 0 Citação(ões) na Scopus
    Comparison of acute kidney injury following brain death between male and female rats
    (2023) ARMSTRONG JR., Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; VIDAL-DOS-SANTOS, Marina; ANUNCIACAO, Lucas Ferreira da; OTTENS, Petra J.; CORREIA, Cristiano Jesus; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Hendrik Gerrit Derk; BREITHAUPT-FALOPPA, Ana Cristina
    Background: Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model.Methods: Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37 & DEG;C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. Results: BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051).Conclusion: The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BDfemale kidneys.
  • article 0 Citação(ões) na Scopus
    Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion
    (2024) RICARDO-DA-SILVA, Fernanda Yamamoto; ARMSTRONG-JR, Roberto; RAMOS, Mayara Munhoz de Assis; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano Jesus; OTTENS, Petra J.; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri G. D.; BREITHAUPT-FALOPPA, Ana Cristina
    BackgroundEx vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.MethodsMale and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1 beta levels. Leukocyte infiltration, myeloperoxidase presence, IL-1 beta gene expression, and long-term release in lung culture (explant) were evaluated.ResultsBrain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1 beta levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.ConclusionIn this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality. Ex vivo lung perfusion maintains lung function in lung grafts from brain dead rats, independently of sex;Inflammation is greater in female's lung grafts even after ex vivo perfusion when compared to males. As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.
  • article
    Protective role of 17 beta-estradiol treatment in renal injury on female rats submitted to brain death
    (2021) ARMSTRONG-JR, Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; VIDAL-DOS-SANTOS, Marina; CORREIA, Cristiano de Jesus; ANUNCIACAO, Lucas Ferreira; SILVA, Raphael dos Santos Coutinho e; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri Gerrit Derk; BREITHAUPT-FALOPPA, Ana Cristina
    Background: Clinical and experimental data highlight the consequences of brain death on the quality of organs and demonstrate the importance of donor state to the results of transplantation. Female rats show higher cardio-pulmonary injury linked to decreased concentrations of female sex hormones after brain-dead (BD). This study evaluated the effect of 17 beta-estradiol on brain death induced renal injury in female rats. Methods: Female Wistar rats were randomically allocated into 4 groups: false-operation (Sham), BD, treatment with 17 beta-estradiol (50 mu g/mL, 2 mL/h) 3 h after brain death (E2-T3), or immediately after brain death confirmation (E2-T0). Creatinine, urea, cytokines, and complement system components were quantified. Renal injury markers, such as KIM-1, Caspase-3, BCL-2 and MMP2/9 were evaluated. Results: Brain death leads to increased kidney KIM-1 expression and longer 17 beta-estradiol treatment resulted in downregulation (P<0.0001). There was increase of neutrophil numbers in kidney from BD rats and E2 treatment was able to reduce it (P=0.018). Regarding complement elements, E2-T3 group evidenced E2 therapeutic effects, reducing C5b-9 (P=0.0004), C3aR (P=0.054) and C5aR (P=0.019). In parallel, there were 17 beta-estradiol effects in reducing MMP2 (P=0.0043), MMP9 (P=0.011), and IL-6 (P=0.024). Moreover, E2-T3 group improved renal function in comparison to BD group (P=0.0938). Conclusions: 17 beta-estradiol treatment was able to reduce acute kidney damage in BD female rats owing to its ability to prevent tissue damage, formation of C5b-9, and local synthesis of inflammatory mediators.
  • conferenceObject
    ESTRADIOL TREATMENT MODULATES ESTRADIOL RECEPTORS EXPRESSION AND REDUCES RENAL INJURY AFTER BRAIN DEATH IN FEMALE RATS
    (2021) CORREIA, Cristiano; ARMSTRONG- JR., Roberto; RICARDO-DA-SILVA, Fernanda Yamamoto; VIDAL-DOS-SANTOS, Marina; ANUNCIACAO, Lucas Ferreira Da; MOREIRA, Luiz Felipe Pinho; LEUVENINK, Henri; BREITHAUPT-FALOPPA, Ana Cristina
  • article 21 Citação(ões) na Scopus
    Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, Three Rs Strategies, and Harm-Benefit Analysis
    (2017) LIGUORI, Gabriel R.; JERONIMUS, Bertus F.; LIGUORI, Tacia T. de Aquinas; MOREIRA, Luiz Felipe P.; HARMSEN, Martin C.
    Animal experimentation requires a solid and rational moral foundation. Objective and emphatic decision-making and protocol evaluation by researchers and ethics committees remain a difficult and sensitive matter. This article presents three perspectives that facilitate a consideration of the minimally acceptable standard for animal experiments, in particular, in tissue engineering (TE) and regenerative medicine. First, we review the boundaries provided by law and public opinion in America and Europe. Second, we review contemporary moral theory to introduce the Neo-Rawlsian contractarian theory to objectively evaluate the ethics of animal experiments. Third, we introduce the importance of available reduction, replacement, and refinement strategies, which should be accounted for in moral decision-making and protocol evaluation of animal experiments. The three perspectives are integrated into an algorithmic and graphic harm-benefit analysis tool based on the most relevant aspects of animal models in TE. We conclude with a consideration of future avenues to improve animal experiments.