MARIA CLAUDIA COSTA IRIGOYEN

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/65, Hospital das Clínicas, Faculdade de Medicina

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  • article 17 Citação(ões) na Scopus
    The role of the baroreflex and parasympathetic nervous system in fructose-induced cardiac and metabolic alterations
    (2018) SANTOS, Fernando dos; MORAES-SILVA, Ivana C.; MOREIRA, Edson D.; IRIGOYEN, Maria-Claudia
    It is well-established that baroreflex sensitivity is essential for blood pressure control, and also plays a key role in the modulation of disease-induced metabolic alterations. In order to investigate the role of the baroreflex in the cardiometabolic and inflammatory derangements promoted by fructose overload, Wistar rats underwent sinoaortic denervation (SAD) or sham surgery and were studied 90 days after receiving tap water (Den and Ctrl) or a 10% fructose solution (Fruc and Den-Fruc). All experimental groups showed marked and similar degree of baroreflex impairment compared to Ctrl. As expected, fructose overload effectively induced metabolic syndrome; however, when it was associated with SAD, several alterations were attenuated. While Fruc rats displayed increased sympathetic modulation and tone and reduced vagal modulation compared to Ctrl animals, Den-Fruc rats showed greater vagal tone and modulation when compared to the Fruc group. Moreover, the Den-Fruc group showed augmented expression of beta 1 adrenergic receptors and TNF/IL-10 ratio and reduction of beta 2 in the left ventricle. The increase in vagal function was correlated with improved insulin sensitivity (r(2)= 0.76), and decreased abdominal fat (r(2)= -0.78) and beta 2 receptors (r(2) = -0.85). Our results showed that: (1) chronic fructose overload induced severe baroreflex impairment, i.e. in a similar magnitude to that observed in SAD rats, which is accompanied by cardiometabolic dysfunctions; (2) the compensatory enhancement in parasympathetic function in SAD rats submitted to fructose intake may point out the possibility of use of approaches that improve vagal function as therapeutic target to attenuate fructose-induced cardiometabolic dysfunctions.
  • article 13 Citação(ões) na Scopus
    Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial
    (2018) FELAU, Sheylla M.; SALES, Lucas P.; SOLIS, Marina Y.; HAYASHI, Ana Paula; ROSCHEL, Hamilton; SA-PINTO, Ana Lucia; ANDRADE, Danieli Castro Oliveira de; KATAYAMA, Keyla Y.; IRIGOYEN, Maria Claudia; CONSOLIM-COLOMBO, Fernanda; BONFA, Eloisa; GUALANO, Bruno; BENATTI, Fabiana B.
    Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (omega-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, omega-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, rho = 0.06, ES = 0.9; and +23 vs. -22%, rho = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (rho > 0.05). In addition, omega-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, rho = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, rho = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, rho = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.
  • article 16 Citação(ões) na Scopus
    Baroreflex Impairment Precedes Cardiometabolic Dysfunction in an Experimental Model of Metabolic Syndrome: Role of Inflammation and Oxidative Stress
    (2018) BERNARDES, Nathalia; DIAS, Danielle da Silva; STOYELL-CONTI, Filipe Fernandes; BRITO-MONZANI, Janaina de Oliveira; MALFITANO, Christiane; CALDINI, Elia Garcia; ULLOA, Luis; LLESUY, Susana Francisca; IRIGOYEN, Maria-Claudia; ANGELIS, Katia De
    This study analyzes whether autonomic dysfunction precedes cardiometabolic alterations in spontaneously hypertensive rats (SHR) with fructose overload. Animals were randomly distributed into three groups: control, hypertensive and hypertensive with fructose overload. Fructose overload (100 g/L) was initiated at 30 days old, and the animals (n = 6/group/time) were evaluated after 7,15, 30 and 60 days of fructose consumption. Fructose consumption reduced baroreflex sensitivity by day 7, and still induced a progressive reduction in baroreflex sensitivity over the time. Fructose consumption also increased TNF alpha and IL-6 levels in the adipose tissue and IL-1 beta(3 levels in the spleen at days 15 and 30. Fructose consumption also reduced plasmatic nitrites (day 15 and 30) and superoxide dismutase activity (day 15 and 60), but increased hydrogen peroxide (day 30 and 60), lipid peroxidation and protein oxidation (day 60). Fructose consumption increased arterial pressure at day 30 (8%) and 60 (11%). Fructose consumption also induced a late insulin resistance at day 60, but did not affect glucose levels. In conclusion, the results show that baroreflex sensitivity impairment precedes inflammatory and oxidative stress disorders, probably by inducing hemodynamic and metabolic dysfunctions observed in metabolic syndrome.
  • article 30 Citação(ões) na Scopus
    Combined Aerobic and Resistance Exercise Training Improve Hypertension Associated With Menopause
    (2018) SHIMOJO, Guilherme Lemos; DIAS, Danielle da Silva; MALFITANO, Christiane; SANCHES, Iris Callado; LLESUY, Susana; ULLOA, Luis; IRIGOYEN, Maria-Claudia; ANGELIS, Katia De
    The prevalence of hypertension sharply increases in menopausal women. Recent studies have demonstrated that aerobic or resistance training may help control hypertension. In this study, we report that combining aerobic and resistance training may provide an effective therapeutic approach for hypertension control, attenuating inflammation and oxidative stress in ovariectomized rats. Female Wistar and spontaneous hypertensive rats (SHR) were distributed into four groups: sedentary control (C), sedentary hypertensive (HR), sedentary hypertensive ovariectomized (HRO), and combined trained hypertensive ovariectomized (T-HR-O). Combined exercise training was performed on a motor treadmill (aerobic training) and on a ladder adapted to rats (resistance training), in alternate days for 8 weeks. Direct arterial pressure was recorded and oxidative stress and inflammation were evaluated in cardiac and renal tissue. Ovariectomy increases increased mean arterial blood pressure, sympathetic modulation, and oxidative stress in SHR. Combining aerobic and resistance training reduced mean arterial blood pressure (12% vs. HR-O), heart rate (8% vs. HR-O), vascular sympathetic modulation (40% vs. HR-O), and improved baroreflex sensitivity. Combined training reduced cardiac inflammation (TNF and IL-6) and cardiac and renal lipoperoxidation (59% and 57%, respectively vs. HR-O). It also enhanced cardiac (71%) and renal (76%) total antioxidant capacity when compared to HRO group. In conclusion, combining aerobic and resistance training improves mean arterial blood pressure, cardiovascular autonomic control, preventing cardiac and renal oxidative stress and inflammation in an experimental hypertension model with surgical menopause induced with ovariectomy.
  • article 4 Citação(ões) na Scopus
    Familial history of hypertension-induced impairment on heart rate variability was not observed in strength-trained subjects
    (2018) SANTA-ROSA, F. A.; SHIMOJO, G. L.; SARTORI, M.; ROCHA, A. C.; V, J. Francica; PAIVA, J.; IRIGOYEN, M. C.; ANGELIS, K. De
    Family history of hypertension is an important predictive factor for hypertension and is associated with hemodynamic and autonomic abnormalities. Previous studies reported that strength training might reduce arterial blood pressure (AP), as well as improve heart rate variability (HRV). However, the benefits of strength training in the offspring of hypertensive parents have not been fully evaluated. Here, we analyzed the impact of strength training on hemodynamics and autonomic parameters in offspring of hypertensive subjects. We performed a cross-sectional study with sedentary or physically active offspring of normotensives (S-ON and A-ON) or hypertensives (S-OH and A-OH). We recorded RR interval for analysis of HRV. AP was similar between groups. Sedentary offspring of hypertensives presented impairment of total variance of RR interval, as well as an increase in cardiac sympathovagal balance (S-OH: 4.2 +/- 0.7 vs S-ON: 2.8 +/- 0.4 and A-ON: 2.4 +/- 0.1). In contrast, the strength-trained group with a family history of hypertension did not show such dysfunctions. In conclusion, sedentary offspring of hypertensives, despite displaying no changes in AP, showed reduced HRV, reinforcing the hypothesis that autonomic dysfunctions have been associated with higher risk of hypertension onset. Our findings demonstrated that strength-trained offspring of hypertensives did not present impaired HRV, thus reinforcing the benefits of an active lifestyle in the prevention of early dysfunctions associated with the onset of hypertension in predisposed populations.
  • conferenceObject
    Baroreflex Sensitivity and Mortality in Septic dysfunction
    (2018) SANTOS, Fernando dos; NOGUEIRA, Antonio Carlos; BISELLI, Paolo; HOSHINO, Wagner; MOSTARDA, Cristiano Teixeira; ANGELIS, Katia De; SORIANO, Francisco Garcia; IRIGOYEN, Maria Claudia
  • article 2 Citação(ões) na Scopus
    beta-blockers interfere with cell homing receptors and regulatory proteins in a model of spontaneously hypertensive rats
    (2018) EIBEL, Bruna; KRISTOCHEK, Melissa; PERES, Thiago R.; DIAS, Lucinara D.; DARTORA, Daniela R.; CASALI, Karina R.; KALIL, Renato A. K.; LEHNEN, Alexandre M.; IRIGOYEN, Maria Claudia; MARKOSKI, Melissa M.
    AimTo examine the interference of -blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7, and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol, and propranolol for 30days using an orogastric tube to hypertensive rats. MethodWe collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme-linked immunosorbent assay (ELISA). On day 30 of treatment, the spontaneously hypertensive rats (SHR) were euthanized, and heart, liver, lung, and kidney tissues were biopsied. Proteins were isolated for determining the expression of CXCR-4, CXCR-7, GRK-2 (G protein-coupled receptors kinase 2), -arrestins (1-AR and 2-AR), and nuclear factor kappa B (NFB). ResultsWe found that the study drugs modulated these proteins, and metoprolol and propranolol strongly affected the expression of 1-AR (P=.0102) and 2-AR (P=.0034). Conclusion-blockers modulated tissue expression of the proteins and their interactions following 30days of treatment. It evidences that this class of drugs can interfere with proteins of cell homing pathways.
  • article 8 Citação(ões) na Scopus
    Measurement of Mouse Heart Rate Variability using Echocardiographic System
    (2018) STOYELL-CONTI, Filipe Fernandes; SANTOS, Fernando; MACHI, Jacqueline Freire; HERNANDEZ, Diana Rosa; BARBOZA, Catarina Andrade; IRIGOYEN, Maria-Claudia; ANGELIS, Katia De; MORRIS, Mariana
    Aim: We employed an echocardiographic (ECHO) system as the backbone for the collection of electrocardiogram (ECG) and heart rate variability (HRV) data. The system was tested using an exercise model in which C57 male mice were exposed to sham or forced wheel running. Methods: Peak/peak (RR) interval was recorded over a 3 min period using the ECG platform of the ECHO system. Isoflurane-anesthetized male mice were divided into two groups (n = 8/group): sedentary (S) and forced wheel trained (T). HRV was analyzed in time and frequency domains (Fast Fourier Transform). Exercise training (T) was performed on a motorized wheel at low intensity 1 h/day, 5 days/week, 8 weeks duration. Cardiac morphometry and function were analyzed using ECHO while ECG was the basis to measure HRV. The sampling rate was 8000 Hz. Results show that the trained mice presented a reduction in heart rate as compared to the sedentary group. This was associated with lower cardiac sympathetic and higher parasympathetic modulation leading to an improved sympathetic/parasympathetic ratio (low-frequency band/high-frequency band). The trained group showed a reduction in isovolumetric relaxation time, reduced myocardial performance index, increased relative wall thickness, and left ventricle mass when compared to the sedentary group. Conclusion: Results document the utility of combining the ECHO and the ECG platform, allowing for the dual measurement of autonomic and cardiac function in mice.
  • conferenceObject
    EFFECT OF SUPPLEMENTATION OF FRUIT EXTRACT (CRANBERRRY, BLUEBERRY AND POMEGRANATE) ON INSULIN RESISTANCE AND OXIDATIVE STRESS IN HYPERTENSIVE PATIENTS
    (2018) GAETA, L. N. N.; MORAES, M. C.; KATAYAMA, K. Y.; SANGALETTI, C. T.; IRIGOYEN, M. C.; FREITAS, S.; VIANA, A.; ANGELIS, K. De; LOPES, H. F.; CALDINI, Elia C.
  • conferenceObject
    PROINFLAMMATORY ROLE OF ANGIOTENSIN II IN THE AORTA OF NORMOTENSIVE MICE
    (2018) LIMA, R. S.; SILVA, J. C. S.; LIMA, C. T.; SOUZA, L. E.; BALADI, M. G.; IRIGOYEN, M. C.; LACCHINI, S.