FRANCISCO RAFAEL MARTINS LAURINDO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
157 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 157
- Time-Dependent Effects of Training on Cardiovascular Control in Spontaneously Hypertensive Rats: Role for Brain Oxidative Stress and Inflammation and Baroreflex Sensitivity(2014) MASSON, Gustavo S.; COSTA, Tassia S. R.; YSHII, Lidia; FERNANDES, Denise C.; SOARES, Pedro Paulo Silva; LAURINDO, Francisco R.; SCAVONE, Cristoforo; MICHELINI, Lisete C.Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-kappa B content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172 +/- 3 mmHg), pressure variability and heart rate (358 +/- 7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47(phox) and reactive oxygen species production, elevated NF-kappa B activity and increased TNF-alpha and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04 +/- 0.31 vs. 2.31 +/- 0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall.
- Translational Medicine and Implementation Science: How to Transform What We Know Into What We Do(2022) LUZ, Protasio Lemos da; LAURINDO, Francisco Rafael Martins
conferenceObject Reflex modulation of vasomotor sympathetic and peripheral autonomic control on hypertension: Sequential effects of aerobic training(2020) MASSON, Gustavo Santos; FERNANDES, Denise; YSHII, Lidia; SOARES, Pedro Paulo; LAURINDO, Francisco R.; SCAVONE, Cristoforo; MICHELINIL, Lisete C.- 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 AlvesBACKGROUND: 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.
- Transit of H2O2 across the endoplasmic reticulum membrane is not sluggish(2016) APPENZELLER-HERZOG, Christian; BANHEGYI, Gabor; BOGESKI, Ivan; DAVIES, Kelvin J. A.; DELAUNAY-MOISAN, Agnes; FORMAN, Henry Jay; GOERLACH, Agnes; KIETZMANN, Thomas; LAURINDO, Francisco; MARGITTAI, Eva; MEYER, Andreas J.; RIEMER, Jan; RUTZLER, Michael; SIMMEN, Thomas; SITIA, Roberto; TOLEDANO, Michel B.; TOUW, Ivo P.Cellular metabolism provides various sources of hydrogen peroxide (H2O2) in different organelles and compartments. The suitability of H2O2 as an intracellular signaling molecule therefore also depends on its ability to pass cellular membranes. The propensity of the membranous boundary of the endoplasmic reticulum (ER) to let pass H2O2 has been discussed controversially. In this essay, we challenge the recent proposal that the ER membrane constitutes a simple barrier for H2O2 diffusion and support earlier data showing that (i) ample H2O2 permeability of the ER membrane is a prerequisite for signal transduction, (ii) aquaporin channels are crucially involved in the facilitation of H2O2 permeation, and (iii) a proper experimental framework not prone to artifacts is necessary to further unravel the role of H2O2 permeation in signal transduction and organelle biology.
conferenceObject Beneficial effects of physical exercise on functional capacity and skeletal muscle oxidative stress in rats with aortic stenosis-induced heart failure(2016) GOMES, M. J.; MARTINEZ, P. F.; PAGAN, L. U.; LIMA, A. R. R.; DAMATTO, R. L.; CEZAR, M. D. M.; FERNANDES, A. A. H.; FERNANDES, D. C.; LAURINDO, F. R.; OKOSHI, K.; OKOSHI, M. P.conferenceObject Lifestyle in wine drinkers and abstemious: the relationship of coronary lesions, calcium score and risk factors(2012) MOCHIDUKY, Roberta I.; ROCHITTE, Carlos E.; FAVARATO, Desiderio; ALBUQUERQUE, Cicero P.; GONSALVES, Cibele Regina L.; LAURINDO, Francisco Rafael M.; HUEB, Whady A.; LUZ, Protasio DaIntroduction: Red wine (RW) protects the cardiovascular system but objective evidence based on coronary status is lacking. Objectives: To assess the effects of chronic RW consumption upon coronary lesion burden. Methods: We performed Coronary Computed Tomographic Angiography in 204 male subjects whose mean age was 58.95±7.3 years and related lesions to risk factors (RF). One hundred were chronic RW drinkers who consumed at least one glass of RW wine/day, 4 –5 times/week, in the last 5 years and 104 were abstemious. Results: RW drinkers consumed 25.78 gr alcohol/day vs 0 among abstemious; they also ingested more calories (2118.50kcal vs 1776.21kcal daily; p<0.01) mainly from saturated fats (22.98 g vs16.51g; p<0.05) than abstemious. Abstemious, however, ingested more fibers (22.73 gr vs17.49 gr; p<0.05). There were no significant differences regarding age, smoking, BMI, arterial hypertension, diabetes, LDL and triglycerides. Psychological factors including anxiety, depression and stress also were similar. However, plasma glucose was lower (97.5±18.3 mg% vs105.9±32.0 mg %; p<0.06) and HDL was higher (46.9±10.9 mg% vs 39.5±9.0 mg%;p<0.01) in RW drinkers compared to abstemious. Calcium score was higher on RW drinkers than in abstemious(144.43±362.2 vs 122.05±370.26; p<0.004). Lesions were classified as absent or 50%. Considering LM, ADA, RCA and Cx in proximal, median and distal portions, plus 3 marginal, 3 diagonal and 2 terminal RCA branches, 3672 segments were included in the analysis. There were no significant differences regarding lesions severity between groups, except for more frequent zero lesions in proximal Cx (86.3 x 71.4 %; p<0.016). Conclusion: Despite higher caloric intake and saturated fats, RW drinkers have similar coronary lesion burden; calcium score, however, was higher compared to abstemious. Higher HDL cholesterol as cribed to RW drinking and lower plasma glucose may have protective roles.- Golgi-independent routes support protein disulfide isomerase externalization in vascular smooth muscle cells(2017) ARAUJO, Thais L. S.; FERNANDES, Carolina G.; LAURINDO, Francisco R. M.Extracellular pools of intracellular molecular chaperones are increasingly evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and vascular remodeling, while PDI externalization routes remain elusive. In endothelial cells, vesicular-type PDI secretion involves classical and unconventional pathways, while in platelets PDI exocytosis involves actin cytoskeleton. However, little is known about pecPDI in vascular smooth muscle cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI pool, which binds to cs independently of electrostatic forces. However, contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC. Calcium ionophore A23187 and TNF alpha enhanced VSMC csPDI. Furthermore, VSMC PDI externalization occurred via Golgi-bypass unconventional route, which was independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild-type mice aortas but markedly enhanced in PDI-overexpressing mice. Such characterization of VSMC pecPDI reinforces cell-type and context specific routes of PDI externalization.
- Unfolded Protein Response: Cause or Consequence of Lipid and Lipoprotein Metabolism Disturbances?(2019) PINTO, Bruno Araujo Serra; FRANCA, Lucas Martins; LAURINDO, Francisco Rafael Martins; PAES, Antonio Marcus de AndradeThe liver plays a capital role in the control of whole body energy homeostasis through the metabolization of dietary carbohydrates and lipids. However, under excess macronutrient uptake, those pathways overcharge nucleus-to-endoplasmic reticulum (ER) traffic pathways, leading to luminal overload of unfolded proteins which activates a series of adaptive signaling pathways known as unfolded protein response (UPR). The UPR is a central network mechanism for cellular stress adaptation, however far from a global nonspecific all-or-nothing response. Such a complex signaling network is able to display considerable specificity of responses, with activation of specific signaling branches trimmed for distinct types of stimuli. This makes the UPR a fundamental mechanism underlying metabolic processes and diseases, especially those related to lipid and carbohydrate metabolism. Thus, for a better understanding of the role of UPR on the physiopathology of lipid metabolism disorders, the concepts discussed along this chapter will demonstrate how several metabolic derangements activate UPR components and, in turn, how UPR triggers several metabolic adaptations through its component signaling proteins. This dual role of UPR on lipid metabolism will certainly foment the pursuit of an answer for the question: is UPR cause or consequence of lipid and lipoprotein metabolism disturbances?
- Nitroarachidonic Acid (NO(2)AA) Inhibits Protein Disulfide Isomerase (PDI) Through Reversible Covalent Adduct Formation with Critical Cysteine Residues(2016) GONZALEZ-PERILLI, Lucia; MASTROGIOVANNI, Mauricio; FERNANDES, Denise; RUBBO, Homero; LAURINDO, Francisco; TROSTCHANSKY, Andres