JOSE EDUARDO KRIEGER

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Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 101 Citação(ões) na Scopus
    Circulating Dipeptidyl Peptidase IV Activity Correlates With Cardiac Dysfunction in Human and Experimental Heart Failure
    (2013) SANTOS, Leonardo dos; SALLES, Thiago A.; ARRUDA-JUNIOR, Daniel F.; CAMPOS, Luciene C. G.; PEREIRA, Alexandre C.; BARRETO, Ana Luiza T.; ANTONIO, Ednei L.; MANSUR, Alfredo J.; TUCCI, Paulo J. F.; KRIEGER, Jose E.; GIRARDI, Adriana C. C.
    Background The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. Methods and Results Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of approximate to 130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (approximate to 50%) and heart tissue (approximate to 3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. Conclusions Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.
  • article
    Modelo porcino para avaliação e desenvolvimento de diferentes dispositivos coronários baseados em cateter: ferramenta pré-clínica fundamental
    (2013) GALON, Micheli Zanotti; TAKIMURA, Celso Kiyochi; CHAVES, Márcio J. Figueira; CAMPOS, Julliana Carvalho de; KRIEGER, J. Eduardo; GUTIERREZ, Paulo Sampaio; LAURINDO, Francisco Rafael Martins; KALIL FILHO, Roberto; LEMOS NETO, Pedro Alves
    BACKGROUND: The experimental porcine model is anatomically and physiologically similar to the human heart, it is easily reproducible and very useful to test new stent and balloon generations. This study was aimed at analyzing an experimental model to evaluate different coronary devices for percutaneous coronary intervention. METHODS: We evaluated 131 juvenile commercial farm pigs, 109 were female, weighing 26.4 ± 3.2 kg. They were anesthetized and had mechanical ventilation and monitoring. Vascular access was obtained via the femoral artery by dissection or puncture. The coronary device was used after a selective catheterization of the coronary arteries with a JR 6 F catheter. Animals were maintained on mechanical ventilation until recovery and were submitted to angiographic evaluation 7, 28, 90 and/or 180 days after the procedure. After euthanasia, the hearts were collected and submitted to macro and microscopic analysis. RESULTS: Six drug-eluting stents, two drug-eluting balloons and two bare-metal stents were tested. Unplanned deaths were observed in 1.5% of the cases during the procedures and in 9.2% of the cases after the procedure, occurring within 12 hours to 6 days (2.3 ± 1.6 days). In addition to angiographic evaluations, intravascular ultrasound and optical coherence tomography were performed during the procedures in 20% and 60% of the cases, respectively. There was no deaths related to the use of the devices. CONCLUSIONS: The experimental percutaneous porcine model proved to be reproducible with similar outcomes and low mortality for the different devices tested and is an essential tool for the evaluation of new coronary devices.
  • article 42 Citação(ões) na Scopus
    Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population
    (2013) ALVIM, Rafael de Oliveira; SANTOS, Paulo Caleb Junior Lima; MUSSO, Mariane Manso; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre Costa
    Background: Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods: A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV >= 12 m/s. Results: In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions: These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
  • article 1 Citação(ões) na Scopus
    Self-declared ethnicity associated with risk factors of cardiovascular diseases in an urban sample of the Brazilian population: The role of educational status in the association
    (2013) SANTOS, H. C.; FRAGOSO, T. M.; MACHADO-COELHO, G. L.; NASCIMENTO, R. M. do; MILL, J. G.; KRIEGER, J. E.; PEREIRA, A. C.
  • conferenceObject
    Selection of candidate genes for hypertension on rat chromosome 4 from shr using expression profilling in kidney and subcongenic strain development
    (2013) TEIXEIRA, Samantha Kuwada; RODRIGUES, Mariliza Velho; MORALES, Marcelo Marcos; KRIEGER, Jose Eduardo
  • article 1 Citação(ões) na Scopus
    O grau de melhora na função das células progenitoras endoteliais derivadas da medula óssea é dependente do volume de treinamento físico aeróbio
    (2013) FERNANDES, Tiago; HASHIMOTO, Nara Yumi; SCHETTERT, Isolmar Tadeu; NAKAMUTA, Juliana Sanajotti; KRIEGER, Jose Eduardo; OLIVEIRA, Edilamar Menezes de
    Introduction: Skeletal muscle angiogenesis induced by aerobic exercise training (ET) is crucial in the improvement of the aerobic capacity. The endothelial progenitor cells (EPC) derived from bone marrow have been described for promoting both the vascular repair and angiogenesis. Although the role of the ET on the parameters of the EPC has been investigated, the effect of different volumes of ET on the EPC function in bone marrow, skeletal muscle metabolic alterations and capillarization are unknown. Objective: We hypothesized that ET improves the EPC function in bone marrow, accompanied by increase of skeletal muscle oxidative capacity and angiogenesis dependents of the increase of volume of ET. Methods: Twenty-one Wistar rats were divided into 3 groups: sedentary control (SC), trained protocol 1 (T1) and trained protocol 2 (T2). T1: swimming training consisted of 60 min, 1x/day/10 weeks, with 5% body weight load. T2 the same as T1 until 8(th) week, in the 9(th) week the rats trained 2x/day and in the 10(th) week 3x/day. Results: ET promoted resting bradycardia, increase of exercise tolerance, peak oxygen uptake and citrate synthase enzyme activity in the T1 group, being these adaptive responses exacerbate in the P2 group, indicating that the aerobic condition was improved in this group. ET improved the EPC function of the bone marrow in T1, and the response was exacerbated in T2 group. In parallel, increase in the number of capillaries dependent of ET volume was also observed. Conclusion: These findings suggest that the bone marrow as the main reservoir of EPC is influenced by different ET volume, possibly being responsible for the improvement of aerobic performance observed by higher endogenous EPC mobilization, active participants in the process of angiogenesis induced by ET.
  • article 35 Citação(ões) na Scopus
    Shear stress-induced Ang II AT1 receptor activation: G-protein dependent and independent mechanisms
    (2013) BARAUNA, Valerio G.; MAGALHAES, Flavio C.; CAMPOS, Luciene C. G.; REIS, Rosana I.; KUNAPULI, Satya P.; COSTA-NETO, Claudio M.; MIYAKAWA, Ayumi A.; KRIEGER, Jose E.
    Mechanotransduction enables cells to sense and respond to stimuli, such as strain, pressure and shear stress (SS), critical for maintenance of cardiovascular homeostasis or pathological states. The angiotensin II type 1 receptor (AT1R) was the first G protein-coupled receptor described to display stretch-induced activation in cardiomyocytes independent of its ligand Ang II. Here, we assessed whether SS (15 dynes/cm(2), 10 min), an important mechanical force present in the cardiovascular system, activates AT1R independent of its ligand. SS induced extracellular signal-regulated kinase (ERIC) activation, used as a surrogate of AT1R activation, in Chinese hamster ovary cells expressing the AT1R (CHO + AT1) but not in wild type cells (CHO). AT1R dependent SS-induced ERIC activation involves Ca2+ inflow and activation of G alpha q since Ca2+ chelator EGTA or G alpha q-specific inhibitor YM-254890 decreased SS-induced ERK activation. On the other hand, the activation of JAK-2 and Src, two intracellular signaling molecules independent of G protein activation, were not differently modulated in the presence of AT1R. Also, ERIC activation by SS was observed in CHO cells expressing the mutated AT1R DRY/AAY, which has impaired ability to activate G alpha q dependent intracellular signaling. Altogether we provided,evidence that SS activates AT1R in the absence of its ligand by both a G protein-dependent and -independent pathways. The biological relevance of these observations deserves to be further investigated since the novel mechanisms described extend the knowledge of the activation of GPCRs independent of its traditional ligand.
  • article 5 Citação(ões) na Scopus
    Reversible pulmonary trunk banding: VII. Stress echocardiographic assessment of rapid ventricular hypertrophy in young goats
    (2013) FAVARO, Gustavo A. G.; ASSAD, Renato S.; ABDUCH, Maria C. D.; SILVA, Gustavo J. J.; GOMES, Guilherme S.; ANDRADE, Jose L.; KRIEGER, Jose E.; MOREIRA, Luiz Felipe P.
    Background: Ventricle retraining with abrupt systolic overload can cause myocardial edema and necrosis, followed by late ventricular failure. Intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding. The present study compared ventricle function under dobutamine stress in 2 protocols of systolic overload in young goats. Methods: Nineteen young goats were divided into 3 groups: sham (n = 7; no systolic pressure overload), continuous (n = 6; systolic overload maintained for 96 hours), and intermittent (n = 6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed daily. The myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The goats were then killed for morphologic evaluation. Results: The intermittent group underwent less systolic overload than the continuous group (P <. 05). Nevertheless, both groups had increased right ventricular and septal masses compared with the sham group (P <. 0002). Echocardiography revealed a major increase in right ventricular wall thickness in the intermittent group (+64.8% +/- 23.37%) compared with the continuous group (+43.9% +/- 19.26%; P = .015). Only the continuous group remained with significant right ventricular dilation throughout the protocol (P <. 001). The intermittent group had a significantly better myocardial performance index at the end of the protocol, under resting and dobutamine infusion, compared with the continuous group (P <. 012). Conclusions: Both systolic overload protocols have induced rapid right ventricular hypertrophy. However, only the intermittent group had better preservation of right ventricular function at the end of the protocol, both at rest and during dobutamine infusion. (J Thorac Cardiovasc Surg 2013; 145:1345-51)
  • article 12 Citação(ões) na Scopus
    Cell therapy prevents structural, functional and molecular remodeling of remote non-infarcted myocardium
    (2013) SANTOS, Leonardo dos; GONCALVES, Giovana A.; DAVEL, Ana Paula; SANTOS, Alexandra A.; KRIEGER, Jose E.; ROSSONI, Luciana V.; TUCCI, Paulo J. F.
    Background/objectives: Therapy using bone marrow (BM) cells has been tested experimentally and clinically due to the potential ability to restore cardiac function by regenerating lost myocytes or increasing the survival of tissues at risk after myocardial infarction (MI). In this study we aimed to evaluate whether BM-derived mononuclear cell (MNC) implantation can positively influence the post-MI structural remodeling, contractility and Ca(2+)-handling proteins of the remote non-infarcted tissue in rats. Methods and results: After 48 h of MI induction, saline or BM-MNC were injected. Six weeks later, MI scars were slightly smaller and thicker, and cardiac dilatation was just partially prevented by cell therapy. However, the cardiac performance under hemodynamic stress was totally preserved in the BM-MNC treated group if compared to the untreated group, associated with normal contractility of remote myocardium as analyzed in vitro. The impaired post-rest potentiation of contractile force, associated with decreased protein expression of the sarcoplasmic reticulum Ca2+-ATPase and phosphorylated-phospholamban and overexpression of Na(+)/Ca(2+) exchanger, were prevented by BM-MNC, indicating preservation of the Ca(2+) handling. Finally, pathological changes on remodeled remote tissue such as myocyte hypertrophy, interstitial fibrosis and capillary rarefaction were also mitigated by cell therapy. Conclusions: BM-MNC therapy was able to prevent cardiac structural and molecular remodeling after MI, avoiding pathological changes on Ca(2+)-handling proteins and preserving contractile behavior of the viable myocardium, which could be the major contributor to the improvements of global cardiac performance after cell transplantation despite that scar tissue still exists.
  • article 2 Citação(ões) na Scopus
    Development of a New Approach to Aid in Visual Identification of Murine iPS Colonies Using a Fuzzy Logic Decision Support System
    (2013) BASSANEZE, Vinicius; SACRAMENTO, Chester Bittencourt; FREIRE, Rodolfo; ALENCAR, Patricia Fernandes De; ORTEGA, Neli Regina Siqueira; KRIEGER, Jose Eduardo
    The a priori identification of induced pluripotent stem cells remains a challenge. Being able to quickly identify the most embryonic stem cell-similar induced pluripotent stem cells when validating results could help to reduce costs and save time. In this context, tools based on non-classic logic can be useful in creating aid-systems based on visual criteria. True colonies when viewed at 100x magnification have been found to have the following 3 characteristics: a high degree of border delineation, a more uniform texture, and the absence of a cracked texture. These visual criteria were used for fuzzy logic modeling. We investigated the possibility of predicting the presence of alkaline phosphatase activity, typical of true induced pluripotent stem cell colonies, after 25 individuals, with varying degrees of experience in working with murine iPS cells, categorized the images of 136 colonies based on visual criteria. Intriguingly, the performance evaluation by area under the ROC curve (16 individuals with satisfactory performance), Spearman correlation (all statistically significant), and Cohen's Kappa agreement analysis (all statistically significant) demonstrates that the discriminatory capacity of different evaluators are similar, even those who have never cultivated cells. Thus, we report on a new system to facilitate visual identification of murine-induced pluripotent stem cell colonies that can be useful for staff training and opens the possibility of exploring visual characteristics of induced pluripotent stem cell colonies with their functional peculiarities. The fuzzy model has been integrated as a web-based tool named ""2see-iPS"" which is freely accessed at http://genetica.incor.usp.br/2seeips/.