MARIA CLAUDIA COSTA IRIGOYEN
Projetos de Pesquisa
Unidades Organizacionais
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
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
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
- Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial(2021) SILVA, Leticia Maria Tedesco; CORTES, Antonio; ROSSI, Beatriz; BOLL, Liliana; WACLAWOSKY, Gustavo; EIBEL, Bruna; GONCALVES, Sandro Cadaval; IRIGOYEN, Maria Claudia; MARTINEZ, DenisBackground: Sleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses. Objective: In this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea. Methods: We will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks. Discussion: Our study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings.
- Effects of autonomic nervous system activation on endothelial function in response to acute exercise in hypertensive individuals: study protocol for a randomized double-blind study(2021) WACLAWOVSKY, Gustavo; BOLL, Liliana Fortini Cavalheiro; GOMES NETO, Salvador; IRIGOYEN, Maria Claudia Costa; LEHNEN, Alexandre M.Background: Arterial hypertension has a direct association with endothelial dysfunction and major cardiovascular events. There is evidence showing the benefits of aerobic exercise on flow-mediated dilation (FMD) in hypertensive individuals but little is known about the effect of autonomic nervous system (ANS) activation on FMD of the brachial artery in response to different types of exercise in this specific population. This study aims to examine the effects of ANS activation on FMD of the brachial artery in response to exercise in hypertensive individuals following a session of different types of exercise including aerobic exercise (AE), resistance exercise (RE), or combined exercise (CE). Methods: Thirty-nine hypertensive volunteers aged 35 to 55 years will be randomly assigned to two exercise sessions: AE (40 min on a cycle ergometer at 60% of HR reserve), RE (4 lower limb sets with 12 repetitions at 60% 1-RM for 40 min), or CE (RE for 20 min + AE for 20 min). Each exercise group will be randomized to receive either an alpha 1-adrenergic blocker (doxazosin 0.05 mg/kg(-1)) or placebo. Ultrasound measurement of FMD is performed 10 min before and 10, 40, and 70 min after exercise. ANS activation is monitored using a Finometer and measurements are taken during 10 min before each FMD assessment. Arterial stiffness is assessed by pulse wave velocity (PWV) analysis using a Complior device. Discussion: We expect to demonstrate the effect of ANS activation on FMD of the brachial artery in hypertensive individuals in response to different types of exercise. This study may give some insight on how to improve exercise prescription for hypertension management.
- Acute ingestion of a high-fructose drink impairs vascular autonomic modulation and reflex control of blood pressure in first-degree relatives of diabetic patients(2021) DIPP, T.; MORAES-SILVA, I. C.; SANTOS, F. Dos; CASALI, K. R.; MORRIS, M.; SIGNORI, L. U.; ANGELIS, K. De; ALETTI, F.; IRIGOYEN, M. C.; PLENTZ, R. D. M.; SCHAAN, B. D.First-degree relatives of diabetes patients, despite being euglycemic, presented impaired BRS and exacerbation of sympathetic modulation after ingestion of a high fructose drink when challenged to orthostatic stress. This finding alerts the importance of early autonomic dysfunction even in clinically healthy people, especially in face of a stressful situation.
- Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model(2021) GONCALVES, Livia de Souza; SALES, Lucas Peixoto; SAITO, Tiemi Raquel; CAMPOS, Juliane Cruz; FERNANDES, Alan Lins; NATALI, Jose; JENSEN, Leonardo; ARNOLD, Alexandre; RAMALHO, Lisley; BECHARA, Luiz Roberto Grassmann; ESTECA, Marcos Vinicius; CORREA, Isis; SANT'ANNA, Diogo; CERONI, Alexandre; MICHELINI, Lisete Compagno; GUALANO, Bruno; TEODORO, Walcy; CARVALHO, Victor Henrique; VARGAS, Bianca Scigliano; MEDEIROS, Marisa Helena Gennari; BAPTISTA, Igor Luchini; IRIGOYEN, Maria Claudia; SALE, Craig; FERREIRA, Julio Cesar Batista; ARTIOLI, Guilherme GianniniHistidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.
- The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial(2021) SANGALETI, Carine Teles; KATAYAMA, Keyla Yukari; ANGELIS, Katia De; MORAES, Tercio Lemos de; ARAUJO, Amanda Aparecida; LOPES, Heno F.; CAMACHO, Cleber; BORTOLOTTO, Luiz Aparecido; MICHELINI, Lisete Compagno; IRIGOYEN, Maria Claudia; OLOFSSON, Peder S.; BARNABY, Douglas P.; TRACEY, Kevin J.; PAVLOV, Valentin A.; COLOMBO, Fernanda Marciano ConsolimBackground: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 mu mol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.
- Increased Maximal Expiratory Pressure, Abdominal and Thoracic Respiratory Expansibility in Healthy Yoga Practitioners Compared to Healthy Sedentary Individuals(2021) FETTER, Cláudia; SOUZA, Liliane Appratto de; DARTORA, Daniela Ravizzoni; SCHEIN, Andressa; EIBEL, Bruna; CASALI, Karina; IRIGOYEN, Maria CláudiaAbstract Background Increasing thoracic expansion is effective at reducing blood pressure in hypertensive subjects. Yoga prescribes many respiratory techniques with a growing number of practitioners. However, very little is known whether sedentary or yoga practitioners show measurable differences in their respiratory patterns. Objective This study aims to demonstrate differences between healthy sedentary individuals and healthy yoga practitioners regarding maximal respiratory pressures and thoracic and abdominal respiratory expansibility. Methods Maximal inspiratory and expiratory pressures (MIP and MEP, respectively) were evaluated by manovacuometry, while respiratory expansion was assessed by the cirtometry of abdominal (CA), thoracic xiphoidal (CTX), and thoracic axillary (CTA) circumferences at rest (end expiratory moment) and at full inspiration in healthy sedentary individuals (SED) and yoga practitioners (YOGA). A delta derived from rest and full inspiration measures (ΔCA, ΔCTX, and ΔCTA, respectively), followed by a percentage of each item (ΔCA/CA, ΔCTX/CTX, and ΔCTA/CTA) was then calculated. Groups were compared by means of an unpaired Student’s t-test, with a significance level p < 0.05. Results All respiratory expansion measures were significantly higher in in the YOGA group. A significantly higher MEP (cmH2O) was also detected in yoga practitioners: SED 89.3 ± 19.3 and YOGA 114.7 ± 24.8 ( p = 0.007), along with decreased heart rate at rest (bpm): SED 84±6 and YOGA 74±15 ( p = 0.001). Conclusions Yoga practitioners have shown greater thoracic and abdominal expansion and increased MEP, when compared to healthy sedentary individuals, as well as significantly lower heart rates at rest and body mass index (BMI). However, whether or not these findings are related to respiratory patterns is uncertain.
- Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice(2021) SOUSA, Marciana V.; AMARAL, Andressa G.; FREITAS, Jessica A.; MURATA, Gilson M.; WATANABE, Elieser H.; BALBO, Bruno E.; TAVARES, Marcelo D.; HORTEGAL, Renato A.; ROCON, Camila; SOUZA, Leandro E.; IRIGOYEN, Maria C.; SALEMI, Vera M.; ONUCHIC, Luiz F.Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13-18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
- Physically active routine during COVID-19 pandemic: do not fail to comply with the recommendations for cardiovascular health(2021) FERREIRA, Maycon Junior; IRIGOYEN, Maria Cláudia; ANGELIS, Kátia De
- The Cholinergic Drug Pyridostigmine Alleviates Inflammation During LPS-Induced Acute Respiratory Distress Syndrome(2021) CHOQUE, Pamela Nithzi Bricher; VIEIRA, Rodolfo P.; ULLOA, Luis; GRABULOSA, Caren; IRIGOYEN, Maria Claudia; ANGELIS, Katia De; OLIVEIRA, Ana Paula Ligeiro De; TRACEY, Kevin J.; PAVLOV, Valentin A.; CONSOLIM-COLOMBO, Fernanda MarcianoAcute respiratory distress syndrome (ARDS) is a critical illness complication that is associated with high mortality. ARDS is documented in severe cases of COVID-19. No effective pharmacological treatments for ARDS are currently available. Dysfunctional immune responses and pulmonary and systemic inflammation are characteristic features of ARDS pathogenesis. Recent advances in our understanding of the regulation of inflammation point to an important role of the vagus-nerve-mediated inflammatory reflex and neural cholinergic signaling. We examined whether pharmacological cholinergic activation using a clinically approved (for myasthenia gravis) cholinergic drug, the acetylcholinesterase inhibitor pyridostigmine alters pulmonary and systemic inflammation in mice with lipopolysaccharide (LPS)-induced ARDS. Male C57Bl/6 mice received one intratracheal instillation of LPS or were sham manipulated (control). Both groups were treated with either vehicle or pyridostigmine (1.5 mg/kg twice daily, 3 mg/day) administered by oral gavage starting at 1 h post-LPS and euthanized 24 h after LPS administration. Other groups were either sham manipulated or received LPS for 3 days and were treated with vehicle or pyridostigmine and euthanized at 72 h. Pyridostigmine treatment reduced the increased total number of cells and neutrophils in the bronchoalveolar lavage fluid (BALF) in mice with ARDS at 24 and 72 h. Pyridostigmine also reduced the number of macrophages and lymphocytes at 72 h. In addition, pyridostigmine suppressed the levels of TNF, IL-1 beta, IL-6, and IFN-gamma in BALF and plasma at 24 and 72 h. However, this cholinergic agent did not significantly altered BALF and plasma levels of the anti-inflammatory cytokine IL-10. Neither LPS nor pyridostigmine affected BALF IFN-gamma and IL-10 levels at 24 h post-LPS. In conclusion, treatments with the cholinergic agent pyridostigmine ameliorate pulmonary and systemic inflammatory responses in mice with endotoxin-induced ARDS. Considering that pyridostigmine is a clinically approved drug, these findings are of substantial interest for implementing pyridostigmine in therapeutic strategies for ARDS.
- Effects of sympathectomy on myocardium remodeling and function(2021) JORDAO, Mauricio Rodrigues; PESSOA, Fernanda G.; FONSECA, Keila C. B.; ZANONI, Fernando; SALEMI, Vera M. C.; SOUZA, Leandro E.; RIBEIRO, Orlando N.; FERNANDES, Fabio; IRIGOYEN, Maria Claudia; MOREIRA, Luiz Felipe P.; MADY, Charles; RAMIRES, Felix Jose AlvarezOBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.