PAULO MAGNO MARTINS DOURADO
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conferenceObject Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome(2012) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; CASELLA, Lia B.; DENARDI, Celise; DOURADO, Paulo; SEGRE, Alexandre; ROEVER-BORGES, Leonardo; NEGRAO, Carlos Eduardo; MARANHAO, Raul; CHAGAS, Antonio CarlosIntroduction: Long-term exercise associated with diet changes lipoproteins plasma levels. Objectives: We sought to analize the effects of short-term exercise training without any specific diet (T) on the concentration,composition and functional characteristics of LDL and HDL in patients with metabolic syndrome (MS). Methods: Forty sedentary persons were studied,30 with MS and 10 controls.Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer.LDL and HDL subfractions were obtained by plasma ultracentrifugation 1 and their compositions were analyzed. LDL from control subjects was incubated with HDL2a,HDL3b from the MS patients (before and after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C-phospholipid, 3 H-triglycerides, 14 C-cholesterol and 3 H-cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE the HDL-containing supernatant was counted for radioactivity to verify the HDL ability to accept lipids. 2 Results: T decreased triglycerides (TG) but did not change apoB,apoA-I,LDL-C and HDL-C plasma levels. LDL resistance to oxidation increased (+91%) after T,associated with a decrease in the LDL content of apoB (-16%) and TG (-14%) and in the concentration of the small and dense LDL particles. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MS, before vs. after T (-23% for HDL2a and -18% for HDL3b),associated with an increase in PON1 activity in the MS group (58.3±36.2 before vs.70.7±38.4ng/ml/min after T, p<0.05) and with a significant decrease in the content of total cholesterol (TC) and TG in HDL3b and HDL3c but with an increase in cholesterol ester (CE) in HDL3b. T did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a. Phospholipids and total protein content did not change in all HDL subfractions.T significantly increased free cholesterol and CE transfer from LDE to HDL in MS group to levels similar to those observed in controls. Conclusion: In patients with the MS, T influences the LDL and HDL functionality by earlier changes in molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating the functional aspects of the lipoproteins besides their plasma levelsconferenceObject Treatment with empagliflozin improves cardiac function in infarcted animals associated with increased baroreflex sensitivity(2023) SILVA, B. Da; NASCIMENTO-CARVALHO, B.; SOUZA, L. I. De; SILVA, M. B. Da; MARQUES, J. R.; DOURADO, P. M. M.; CONSOLIM-COLOMBO, F.; IRIGOYEN, M. C. C.- Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure(2017) CAMPOS, Juliane C.; QUELICONI, Bruno B.; BOZI, Luiz H. M.; BECHARA, Luiz R. G.; DOURADO, Paulo M. M.; ANDRES, Allen M.; JANNIG, Paulo R.; GOMES, Katia M. S.; ZAMBELLI, Vanessa O.; ROCHA-RESENDE, Cibele; GUATIMOSIM, Silvia; BRUM, Patricia C.; MOCHLY-ROSEN, Daria; GOTTLIEB, Roberta A.; KOWALTOWSKI, Alicia J.; FERREIRA, Julio C. B.We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterize the impact of exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 wk after myocardial infarction. These changes were accompanied by accumulation of fragmented mitochondria with reduced O-2 consumption, elevated H2O2 release and increased Ca2+-Cinduced mitochondrial permeability transition pore opening. Of interest, disruption of autophagic flux was sufficient to decrease cardiac mitochondrial function in sham-treated animals and increase cardiomyocyte toxicity upon mitochondrial stress. Importantly, 8 wk of exercise training, starting 4 wk after myocardial infarction at a time when autophagy and mitochondrial oxidative capacity were already impaired, improved cardiac autophagic flux. These changes were followed by reduced mitochondrial number: size ratio, increased mitochondrial bioenergetics and better cardiac function. Moreover, exercise training increased cardiac mitochondrial number, size and oxidative capacity without affecting autophagic flux in sham-treated animals. Further supporting an autophagy mechanism for exercise-induced improvements of mitochondrial bioenergetics in heart failure, acute in vivo inhibition of autophagic flux was sufficient to mitigate the increased mitochondrial oxidative capacity triggered by exercise in failing hearts. Collectively, our findings uncover the potential contribution of exercise in restoring cardiac autophagy flux in heart failure, which is associated with better mitochondrial quality control, bioenergetics and cardiac function.
- Endothelial Alterations in Aging(2018) WAJNGARTEN, M.; NUSSBACHER, A.; DOURADO, P. M. M.; CHAGAS, A. C. P.Age is an important modifying factor of endothelial structure and function in humans. Mechanisms involved in the reduction of age-related endothelium-dependent vasodilation are caused mainly by a primary alteration in the l-arginine-NO pathway. Oxidative stress in the arterial wall plays an important role in the elderly, as it compromises NO bioavailability. The compromise of endothelium-dependent vasodilation in hypertension appears to represent an acceleration of the changes seen in aging. Endothelial dysfunction contributes to making vascular aging a strong risk factor for the development of cardiovascular diseases. On the other hand, experimental evidence suggests that dietary restriction stimulates preservation of vascular function through several mechanisms such as sirtuins, AMP kinase, insulin/insulin-like growth factor 1, and TOR kinase protein. However, controversies still remain as to how caloric restriction improves mitochondrial performance and whether this is sufficient to delay cell and age-dependent decline of the organism. © 2018 Elsevier Inc. All rights reserved.
- Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction(2019) BARBOZA, C. A.; FUKUSHIMA, A. R.; CARROZZI, N.; MACHI, J. F.; DOURADO, P. M. M.; MOSTARDA, C. T.; IRIGOYEN, M. C.; NATHANSON, L.; MORRIS, M.; CAPERUTO, E. C.; RODRIGUES, B.Inflammatory processes and cardiovascular autonomic imbalance are very relevant characteristic of the enormous dynamic process that is a myocardial infarction (MI). In this sense, some studies are investigating pharmacological therapies using acetylcholinesterase inhibitors, such as pyridostigmine bromide (PYR), aiming to increase parasympathetic tone after MI. Here we hypothesized that the use of PYR before the MI might bring an additional positive effect to the autonomic function, and consequently, in the inflammatory response and cardiac function. The present study aimed to evaluate left ventricular function, baroreflex sensitivity, autonomic modulation, and inflammatory profile in PYR- treated rats previously to MI. Methods: Male Wistar rats (250-300 g) were treated for 60 days with PYR. After treatment, they were submitted to the MI. After the MI, the autonomic and ventricular function were evaluated, as well as the systemic, left ventricle, and adipose tissue inflammatory profile. Results: PYR, performed before MI, prevented HR increase, systolic function impairment, baroreflex sensitivity drop, as well as pulse interval variance, RMSSD, blood pressure and parasympathetic modulation reduction in treated rats compared to untreated rats. Also, this positive functional changes may have been a result of the reduced inflammatory parameters in the left ventricle (IFN-alpha, IL-6, and IL-1 beta), as well as increased IL-10 expression and IL-10/TNF-alpha ratio in treated animals before MI. Conclusion: Prior treatment with PYR prevents impairment of the autonomic nervous system after MI, which may be associated with the attenuated expression of inflammatory factors and heart dysfunction.
conferenceObject RELATIONSHIPS BETWEEN HDL FUNCTIONAL CHARACTERISTICS AND ENDOTHELIAL VASCULAR FUNCTION AFTER SHORT-TERM EXERCISE TRAINING IN PATIENTS WITH THE METABOLIC SYNDROME(2013) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; DOURADO, Paulo; LEITE-JUNIOR, Antonio C.; JONKE, Vivian; SEGRE, Alexandre; SANTOS, Raul; NEGRAO, Carlos E.; MARANHAO, Raul C.; CHAGAS, AntonioIntroduction: Endothelial dysfunction, leading to vasodilation impairment and atherosclerosis, frequently affects patients with metabolic syndrome (MS). A recent study showed that HDL estimulates endothelial nitric oxide synthase (eNOS: a key regulator of vascular nitric oxide production) by activation of Akt and MAP kinases in cultured endothelial cells. Objectives: To investigate the relationships between HDL characteristics (concentration, composition, functionality) on the eNOS availability and endothelial vascular function in patients with MS after a short-term exercise training (T). Methods: Forty sedentary persons (30 MS and 10 controls) were studied. Twenty with MS were subjected to a 3 times/week of a training load (45min/d) for 3 months on a bicycle. Cyclic guanosine monophosphate (cGMP), blood nitrite concentrations (biomarkers of eNOS availability) and HDL subfractions obtained by plasma ultracentrifugation were analyzed. A control LDL was incubated with HDL subfractions from the patients with MS (before-after T) and the in vitro resistance to oxidation was verified. An artificial radio-labeled lipoprotein emulsion was incubated with plasma from the participants. After precipitation of VLDL and LDL, the HDL containing supernatant was counted for radioactivity, to verify the HDL ability to accept lipids. Endothelial vascular function was assessed from forearm blood flow-mediated responses to vasodilation tests (FMD). Results: T did not change HDL-C concentration but changed the molecular composition and improved the functional characteristics of the HDL-particles subfractions: protecting LDL against oxidation (+21%) and increasing the HDL-particles ability to accept lipids (+23%). T increased cGMP and blood nitrite concentrations. The best HDL functional results were associated with the highest cGMP and blood nitrite concentrations and with the best FMD improvement results in the MS group. Conclusions: T early changes functional characteristics of HDL-particles, rather than HDL-C concentration, associated with eNOS biomarkers and with endothelial vascular function improvement in patients with MS, highlighting the early vascular benefits of exercising- High- versus moderate-intensity aerobic exercise training effects on skeletal muscle of infarcted rats(2013) MOREIRA, Jose B. N.; BECHARA, Luiz R. G.; BOZI, Luiz H. M.; JANNIG, Paulo R.; MONTEIRO, Alex W. A.; DOURADO, Paulo M.; WISLOFF, Ulrik; BRUM, Patricia C.Moreira JB, Bechara LR, Bozi LH, Jannig PR, Monteiro AW, Dourado PM, Wisloff U, Brum PC. High- versus moderate-intensity aerobic exercise training effects on skeletal muscle of infarcted rats. J Appl Physiol 114: 1029-1041, 2013. First published February 21, 2013; doi:10.1152/japplphysiol.00760.2012.-Poor skeletal muscle performance was shown to strongly predict mortality and long-term prognosis in a variety of diseases, including heart failure (HF). Despite the known benefits of aerobic exercise training (AET) in improving the skeletal muscle phenotype in HF, the optimal exercise intensity to elicit maximal outcomes is still under debate. Therefore, the aim of the present study was to compare the effects of high-intensity AET with those of a moderate-intensity protocol on skeletal muscle of infarcted rats. Wistar rats underwent myocardial infarction (MI) or sham surgery. MI groups were submitted either to an untrained (MI-UNT); moderate-intensity (MI-CMT, 60% (V) over dot(O2) (max)); or matched volume, high-intensity AET (MI-HIT, intervals at 85% (V) over dot(O2) (max)) protocol. High-intensity AET (HIT) was superior to moderate-intensity AET (CMT) in improving aerobic capacity, assessed by treadmill running tests. Cardiac contractile function, measured by echocardiography, was equally improved by both AET protocols. CMT and HIT prevented the MI-induced decay of skeletal muscle citrate synthase and hexokinase maximal activities, and increased glycogen content, without significant differences between protocols. Similar improvements in skeletal muscle redox balance and deactivation of the ubiquitin-proteasome system were also observed after CMT and HIT. Such intracellular findings were accompanied by prevented skeletal muscle atrophy in both MI-CMT and MI-HIT groups, whereas no major differences were observed between protocols. Taken together, our data suggest that despite superior effects of HIT in improving functional capacity, skeletal muscle adaptations were remarkably similar among protocols, leading to the conclusion that skeletal myopathy in infarcted rats was equally prevented by either moderate-intensity or high-intensity AET.
bookPart Alterações endoteliais no envelhecimento(2016) WAJNGARTEN, Mauricio; NUSSBACHER, Amit; DOURADO, Paulo Magno Martins; CHAGAS, Antonio Carlos Palandri- Induced pluripotent stem cells reprogramming: Epigenetics and applications in the regenerative medicine(2017) GOMES, Kátia Maria Sampaio; COSTA, Ismael Cabral; SANTOS, Jeniffer Farias dos; DOURADO, Paulo Magno Martins; FORNI, Maria Fernanda; FERREIRA, Julio Cesar BatistaSummary Induced pluripotent stem cells (iPSCs) are somatic cells reprogrammed into an embryonic-like pluripotent state by the expression of specific transcription factors. iPSC technology is expected to revolutionize regenerative medicine in the near future. Despite the fact that these cells have the capacity to self-renew, they present low efficiency of reprogramming. Recent studies have demonstrated that the previous somatic epigenetic signature is a limiting factor in iPSC performance. Indeed, the process of effective reprogramming involves a complete remodeling of the existing somatic epigenetic memory, followed by the establishment of a ""new epigenetic signature"" that complies with the new type of cell to be differentiated. Therefore, further investigations of epigenetic modifications associated with iPSC reprogramming are required in an attempt to improve their self-renew capacity and potency, as well as their application in regenerative medicine, with a new strategy to reduce the damage in degenerative diseases. Our review aimed to summarize the most recent findings on epigenetics and iPSC, focusing on DNA methylation, histone modifications and microRNAs, highlighting their potential in translating cell therapy into clinics.
- Epicardial adipose tissue and carotid artery disease: Protocol for systematic review and meta-analysis(2018) ROEVER, Leonardo; RESENDE, Elmiro Santos; DINIZ, Angelica Lemos Debs; PENHA-SILVA, Nilson; O'CONNELL, Joao Lucas; GOMES, Paulo Fernando Silva; ZANETTI, Hugo Ribeiro; ROERVER-BORGES, Anaisa Silva; VELOSO, Fernando Cesar; SOUZA, Fernanda Rodrigues de; DUARTE, Poliana Rodrigues Alves; FIDALE, Thiago Montes; CASELLA-FILHO, Antonio; DOURADO, Paulo Magno Martins; CHAGAS, Antonio Carlos Palandri; ALI-HASAN-AL-SAEGH, Sadeq; REIS, Paulo Eduardo Ocke; PINTO, Rogerio de Melo Costa; OLIVEIRA, Gustavo B. F.; AVEZUM, Alvaro; NETO, Mansueto; DURAES, Andre; SILVA, Rose Mary Ferreira Lisboa da; GRANDE, Antonio Jose; DENARDI, Celise; LOPES, Renato Delascio; NERLEKAR, Nitesh; ALIZADEH, Shahab; HERNANDEZ, Adrian V.; ROSA, Maria Ines da; BIONDI-ZOCCAI, GiuseppeBackground:Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex.Methods:This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators.Results:We propose the current protocol to evaluate the evaluation of EAT with ED.Conclusion:This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal.Ethics and dissemination:Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal.Trial registration number: PROSPERO (CRD42018083458).