CELSO KIYOCHI TAKIMURA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model(2018) GUIDO, Maria C.; DEBBAS, Victor; SALEMI, Vera M.; TAVARES, Elaine R.; MEIRELLES, Thayna; ARAUJO, Thais L. S.; NOLASCO, Patricia; FERREIRA-FILHO, Julio C. A.; TAKIMURA, Celso K.; PEREIRA, Lygia V.; LAURINDO, Francisco R.Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mg Delta(loxPneo) mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.
- Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect(2016) TANAKA, Leonardo Y.; ARAUJO, Haniel A.; HIRONAKA, Gustavo K.; ARAUJO, Thais L. S.; TAKIMURA, Celso K.; RODRIGUEZ, Andres I.; CASAGRANDE, Annelise S.; GUTIERREZ, Paulo S.; LEMOS-NETO, Pedro Alves; LAURINDO, Francisco R. M.Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (approximate to 25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to impaired viscoelastic ductility. Total and PDI-associated expressions of 1-integrin, and levels of reduced cell-surface 1-integrin, were diminished after PDI antibody treatment, implicating 1-integrin as a likely pecPDI target during vessel repair. Indeed, focal adhesion kinase phosphorylation, a downstream 1-integrin effector, was decreased by PDI antibody. Thus, the upregulated pecPDI pool tunes matrix/cytoskeleton reshaping to counteract inward remodeling in vascular pathophysiology.
conferenceObject A Novel Magnesium Bioresorbable Stent Allows Coronary Vascular Restoration and Positive Remodeling in a Large Animal Model: A Sequential Optical Coherence Tomography Study(2015) TAKIMURA, Celso K.; CAVALCANTI, Rafael R.; GALON, Micheli Z.; ARRIETA, Raul; TELLEZ, Armando; CAMPOS, Carlos M.; CURADO, Luciano; MEYER-KOBBE, Clemens; KRIEGER, Jose E.; LEMOS, Pedro A.- Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter(2013) LEMOS, Pedro A.; FAROOQ, Vasim; TAKIMURA, Celso K.; GUTIERREZ, Paulo S.; VINNANI, Renu; KOLODGIE, Frank; CHRISTIANS, Uwe; KHARLAMOV, Alexander; DOSHI, Manish; SOJITRA, Prakash; BEUSEKOM, Heleen M. M. van; SERRUYS, Patrick W.Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.
- Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction(2017) DARIOLLI, Rafael; NAGHETINI, Marcus V.; MARQUES, Euclydes F.; TAKIMURA, Celso K.; JENSEN, Leonardo S.; KIERS, Bianca; TSUTSUI, Jeane M.; MATHIAS JR., Wilson; LEMOS NETO, Pedro A.; KRIEGER, Jose E.Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose- tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x10 6 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCsinduced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.
- An automatic labeling bifurcation method for Intracoronary Optical Coherence Tomography images(2015) MACEDO, Maysa M. G.; TAKIMURA, Celso K.; LEMOS, Pedro A.; GUTIERREZ, Marco A.Vessel branchings are critical vascular locations from the clinical point of view. In these sites, the arterial hemodynamic plays a relevant role in the progression of atherosclerosis, an important vascular pathology. In this paper, a fully automatic approach for the bifurcation classification in human Intravascular Optical Coherence Tomography (IV-OCT) sequences is introduced. Given the lumen contours, the method is capable of labeling the bifurcation slices. A geometric feature extraction was performed and the Forward Regression Orthogonal Least Squares method (FROLS) was applied to analyze the best features and to determine the appropriated weights in a binary classifier. A cross-validation scheme is applied in order to evaluate the performance of the classification approach and the results have shown a sensitivity of 86% and specificity of 92% to FROLS.
- A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries(2015) TAKIMURA, Celso K.; GALON, Micheli Z.; GUTIERREZ, Paulo S.; SOJITRA, Prakash; VYAS, Ashwin; DOSHI, Manish; LEMOS, Pedro A.Background: Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). Methods: In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. Results: According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. Conclusions: The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies.
- A bifurcation identifier for IV-OCT using orthogonal least squares and supervised machine learning(2015) MACEDO, Maysa M. G.; GUIMARAES, Welingson V. N.; GALON, Micheli Z.; TAKIMURA, Celso K.; LEMOS, Pedro A.; GUTIERREZ, Marco AntonioIntravascular optical coherence tomography (IV-OCT) is an in-vivo imaging modality based on the intravascular introduction of a catheter which provides a view of the inner wall of blood vessels with a spatial resolution of 10-20 mu m. Recent studies in IV-OCT have demonstrated the importance of the bifurcation regions. Therefore, the development of an automated tool to classify hundreds of coronary OCT frames as bifurcation or nonbifurcation can be an important step to improve automated methods for atherosclerotic plaques quantification, stent analysis and co-registration between different modalities. This paper describes a fully automated method to identify IV-OCT frames in bifurcation regions. The method is divided into lumen detection; feature extraction; and classification, providing a lumen area quantification, geometrical features of the cross-sectional lumen and labeled slices. This classification method is a combination of supervised machine learning algorithms and feature selection using orthogonal least squares methods. Training and tests were performed in sets with a maximum of 1460 human coronary OCT frames. The lumen segmentation achieved a mean difference of lumen area of 0.11 mm(2) compared with manual segmentation, and the AdaBoost classifier presented the best result reaching a F-measure score of 97.5% using 104 features.
- Intravascular Ultrasound Guidance to Minimize the Use of Iodine Contrast in Percutaneous Coronary Intervention The MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) Randomized Controlled Trial(2014) MARIANI JR., Jose; GUEDES, Cristiano; SOARES, Paulo; ZALC, Silvio; CAMPOS, Carlos M.; LOPES, Augusto C.; SPADARO, Andre G.; PERIN, Marco A.; ESTEVES FILHO, Antonio; TAKIMURA, Celso K.; RIBEIRO, Expedito; KALIL-FILHO, Roberto; EDELMAN, Elazer R.; SERRUYS, Patrick W.; LEMOS, Pedro A.OBJECTIVES The aim of this study was to evaluate the impact of intravascular ultrasound (IVUS) guidance on the final volume of contrast agent used in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND To date, few approaches have been described to reduce the final dose of contrast agent in PCIs. We hypothesized that IVUS might serve as an alternative imaging tool to angiography in many steps during PCI, thereby reducing the use of iodine contrast. METHODS A total of 83 patients were randomized to angiography-guided PCI or IVUS-guided PCI; both groups were treated according to a pre-defined meticulous procedural strategy. The primary endpoint was the total volume contrast agent used during PCI. Patients were followed clinically for an average of 4 months. RESULTS The median total volume of contrast was 64.5 ml (interquartile range [IQR]: 42.8 to 97.0 ml; minimum, 19 ml; maximum, 170 ml) in the angiography-guided group versus 20.0 ml (IQR: 12.5 to 30.0 ml; minimum, 3 ml; maximum, 54 ml) in the IVUS-guided group (p < 0.001). Similarly, the median volume of contrast/ creatinine clearance ratio was significantly lower among patients treated with IVUS-guided PCI (1.0 [IQR: 0.6 to 1.9] vs. 0.4 [IQR: 0.2 to 0.6, respectively; p < 0.001). In-hospital and 4-month outcomes were not different between patients randomized to angiography-guided and IVUS-guided PCI. CONCLUSIONS Thoughtful and extensive use of IVUS as the primary imaging tool to guide PCI is safe and markedly reduces the volume of iodine contrast compared with angiography-alone guidance. The use of IVUS should be considered for patients at high risk of contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty. (C) 2014 by the American College of Cardiology Foundation.
- Clinical performance of a novel ultrathin strut, low-dose, sirolimus-eluting stent with abluminal-only biodegradable polymeric coating for patients undergoing percutaneous coronary intervention in the daily practice(2015) PRADO JR., Guy F. A.; RIBEIRO, Expedito E.; MELO, Pedro H. M. C.; PINTON, Fabio A.; ESTEVES-FILHO, Antonio; TAKIMURA, Celso K.; MARIANI JR., Jose; KAJITA, Luiz J.; MARCHIORI, Gilberto; FALCAO, Breno de Alencar Araripe; GALON, Micheli Z.; SOARES, Paulo R.; ZALC, Silvio; LEMOS, Pedro A.Background: The present study aimed to evaluate the clinical performance, in the daily practice of a busy catheterization laboratory, of a novel drug-eluting stent (DES) built with an ultra-thin-strut metallic platform, eluting sirolimus at low doses, abluminal coated with biodegradable polymers, and mounted in a low-compliant delivery system. Methods: Prospective, single-arm study, comprising all consecutive patients undergoing percutaneous coronary intervention (PCI) with the Inspiron (TM) sirolimus-eluting stent (SES) (Scitech, Aparecida de Goiania, Brazil). The primary endpoint was the occurrence of major adverse cardiac events (MACE) [cardiac death, non-PCI related myocardial infarction (MI), or target vessel revascularization (TVR)]. Results: A total of 470 patients were included, from which 51.3% were diabetics, 33.8% had triple-vessel disease, 15.3% had heart failure, 38.9% had at least one bifurcation treated, 19.8% were treated for a bare metal stent restenosis, and 61.9% had at least one type C lesion; one or more of these features were found in 96.0%. At 300 days, the rate target lesion revascularization was 5.4% and the rate of MACE was 8.1%. The incidence of definite or probable stent thrombosis was 0.4%, with no cases between 30 and 300 days. Conclusions: The novel stent is associated with excellent short and mid-term clinical outcomes in patients treated with PCI in the daily practice.