HANIEL ALVES ARAUJO
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- 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.
- Normative data of cortical excitability measurements obtained by transcranial magnetic stimulation in healthy subjects(2016) CUEVA, Ana Sofia; GALHARDONI, Ricardo; CURY, Rubens Gisbert; PARRAVANO, Daniella Cardoso; CORREA, Guilherme; ARAUJO, Haniel; CECILIO, Sofia Barros; RAICHER, Irina; TOLEDO, Diego; SILVA, Valquiria; MARCOLIN, Marco Antonio; TEIXEIRA, Manoel Jacobsen; ANDRADE, Daniel Ciampi deObjectives. - To obtain normative data for CE measurements by transcranial magnetic stimulation, to assess inter- /intra-investigator variability and the influence of sex, age and oral contraception use. Methods. - A sample of 216 healthy volunteers matched according to age and gender was evaluated. Bilateral rest motor thresholds, motor evoked potentials (MEP), intracortical inhibition and facilitation were measured in the first dorsal interosseous muscle area representation of the primary motor cortex with a circular transcranial magnetic stimulation coil delivering biphasic pulses. Normative data were obtained for 200 participants (in a 1:1 male:female ratio) in a balanced proportion between five age groups (18-30; 31-40; 41-50; 51-60; > 60 years). Inter/intra-investigator variability was assessed in 20 healthy volunteers in two sessions performed within a 30-minute interval. Measurements were also performed in a subgroup of 16 healthy female volunteers, using oral contraception and during the menstrual phase. Results. - Age had a dichotomous effect on CE measurements, providing significantly different normative data for subjects < 50 and > 50 years old, with smaller MEP's and intracortical inhibition in older individuals. There were no differences between genders or between left and right hemispheres. Also, CE parameters did not significantly differ with use of contraceptive treatment compared to the menstrual phase of the cycle. The inter-/intra-investigator reliability assessment showed some variability that may not be clinically significant. Conclusions. - Age had a non-linear effect on CE. There were non-significant differences between genders, hemispheres or with use of oral contraceptives. There was good inter- /intra-investigator correlation for rest motor thresholds and motor evoked potentials while intracortical inhibition and facilitation had low correlations but acceptable reliability. 2016 Elsevier Masson SAS. All rights reserved.