LEANDRO EZIQUIEL DE SOUZA
Índice h a partir de 2011
7
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout(2016) BALBO, Bruno E.; AMARAL, Andressa G.; FONSECA, Jonathan M.; CASTRO, Isac de; SALEMI, Vera M.; SOUZA, Leandro E.; SANTOS, Fernando dos; IRIGOYEN, Maria C.; QIAN, Feng; CHAMMAS, Roger; ONUCHIC, Luiz F.Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond) Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1(cond/cond):Nestin(cre);Lgals(3-/-) (CYG-) and Pkd1(+/-);Lgals(3-/-) (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single -mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1(v/v); VVG+) showed that Pkd1(v/v);Lgals(3-/-) (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkdl-deficient models and suppression of galectin-3 expression rescues this phenotype.
- 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.
- Cardiovascular autonomic dysfunction in non-obese diabetic mice(2013) MORAES, Oscar A.; COLUCCI, Juliana A.; SOUZA, Leandro E.; SCAPINI, Katia B.; MORAES-SILVA, Ivana C.; MOSTARDA, Cristiano; ANGELIS, Katia De; CASARINI, Dulce E.; IRIGOYEN, Maria ClaudiaIt is known that diabetes is associated with autonomic dysfunction; however, data about autonomic function in non-obese diabetic mice (NOD) remain scarce. We evaluated the autonomic profile of NOD mice. Female mice, 24-28 week old, were divided in two groups: NOD (n = 6) and control (n = 6, Swiss mice). NOD mice with glycemia >= 300 mg/dl were used. Heart rate variability (HRV) and arterial pressure variability (APV) in time and frequency domains, symbolic analysis of heart rate (HR) and baroreflex sensitivity were evaluated. HR and arterial pressure (AP) were similar between the groups; however, HRV (total variance of RR interval: NOD = 21.07 +/- 3.75 vs. C = 42.02 +/- 6.54 ms(2)) and the vagal modulation index RMSSD were lower in NOD group (4.01 +/- 032 vs. 8.28 +/- 0.97 ms). Moreover, the absolute and normalized low-frequency (LF) components were also enhanced in NOD (normalized = 61.0 +/- 4.0%) as compared to control mice (normalized = 20.0 +/- 4.0%). Both the absolute and normalized high-frequency (HF) components were lower in NOD (normalized = 39.0 +/- 4.0%) when compared to the control group (normalized = 80.0 +/- 4.0). In the symbolic analysis the 0V pattern, an indication of sympathetic activity, was higher in NOD and 2LV pattern, an indication of parasympathetic activity, was lower in the NOD than in the control group. Both bradycardic and tachycardic responses were decreased in NOD (3.01 +/- 0.72 vs. 4.54 +/- 0.36 bpm/mm Hg and 2.49 +/- 031 vs. C = 3.43 +/- 033 bpm/mm Hg) when compared to the control group. Correlation analysis showed negative correlations between vagal indexes (RMSSD, %HF and 2LV) and glycemic levels. In conclusion, NOD mice develop severe diabetes correlated with autonomic dysfunction.
- Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice (vol 13, pg 257, 2017)(2017) ABAD, Cesar Cavinato Cal; NASCIMENTO, Ademir Manuel do; SOUZA, Leandro Eziquiel de; FIGUEROA, Diego; RAMONA, Pamella; SARTORI, Michele; SCAPINI, Katia B.; ALBUQUERQUE, Oscar; MORAES-SILVA, Ivana Cinthya; COELHO-JUNIOR, Helio Jose; RODRIGUES, Bruno; MOSTARDA, Cristiano Teixeira; ANGELIS, Katia De; IRIGOYEN, Maria Claudia
- Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats(2020) MOREIRA, Nathalia Juocys Dias; SANTOS, Fernando dos; MOREIRA, Edson Dias; FARAH, Daniela; SOUZA, Leandro Eziquiel de; SILVA, Maikon Barbosa da; MORAES-SILVA, Ivana Cinthya; LINCEVICIUS, Gisele Silverio; CALDINI, Elia Garcia; IRIGOYEN, Maria Claudia CostaMechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive+RDN (ND) or sham surgery (NS), and hypertensive+RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration-response curves to phenylephrine, sodium nitroprusside and acetylcholine (10(-10)-10(-5) M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean +/- SEM. Urinary volume was 112% higher in HD vs. HS (HS=14.94 +/- 2.5 mL; HD=31.69 +/- 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS=201 +/- 12 vs. HD=172 +/- 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS=5.8 +/- 0.7 ms(2) vs. HD=13.4 +/- 1.4 ms(2); HS=3.5 +/- 0.7 ms(2) vs. HD=10.5 +/- 1.7 ms(2), respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.
- Tonin Overexpression in Mice Diminishes Sympathetic Autonomic Modulation and Alters Angiotensin Type 1 Receptor Response(2019) JARA, Zaira Palomino; ICIMOTO, Marcelo Yudi; YOKOTA, Rodrigo; RIBEIRO, Amanda Aparecida; SANTOS, Fernando dos; SOUZA, Leandro Ezequiel de; WATANABE, Ingrid Kazue Mizuno; FRANCO, Maria do Carmo; PESQUERO, Jorge Luiz; IRIGOYEN, Maria Claudia; CASARINI, Dulce ElenaBackground: Tonin, a serine-protease that forms Angiotensin II (AngII) from angiotensinogen, is increased in failing human heart samples. Increased blood pressure (BP) and decreased heart rate (HR) variabilities are associated with higher risk of cardiovascular morbidity. Losartan has been used to reduce hypertension and, therefore, lowers the risk of fatal and non-fatal cardiovascular events. Determination of tonin's impact on BP and HR variabilities as well as the impact of losartan remain questions to be elucidated. Aim: Evaluation of cardiovascular autonomic profile in transgenic mice overexpressing the rat tonin enzyme TGM'(rton) and the impact of AT1 receptor blocker, losartan. Methods: Male C57BL/6 (WT) and TGM'(rTon) mice were cannulated for recording BP (Windaq, 4 MHz) for 30min at baseline and 30min after losartan injection (20 mg/kg). BP and HR variabilities were analyzed in time and frequency domain method. Low-frequency (LF) and high-frequency (HF) components were identified for sympathetic and parasympathetic modulations analysis. Ang I, AngII, and Ang1-7 were quantified by high performance liquid chromatography method. The total enzymatic activity for AngI, AngII, and Ang1-7 formation was evaluated in the heart and plasma by Liquid chromatography mass spectrometry (LC-MS/MS). Results: At the baseline TGM'(rTon) exhibited higher BP, lower cardiac LF, higher cardiac HF, lower LF/HF, and lower alpha index than wild type (WT). After losartan injection, TGM'(rTon) mice presented an additional decrease in cardiac LF and increase in HF in relation to baseline and WT. In the vasculature, losartan caused decreased in BP and LF of systolic BP in WT mice in relation to its baseline. A similar effect was observed in the BP of TGM'(rTon) mice; however, LF of systolic BP increased compared to baseline. Our data also indicates that AT1R receptor signaling has been altered in TGM'(rTon) mice. Interestingly, the dynamics of the renin-angiotensin system kinetics change, favoring production of Ang1-7. Conclusion: Autonomic evaluation of TGM'(rTon) mice indicates an unclear prognosis for diseases that affect the heart. HR variability in TGM'(rTon) mice indicates high risk of morbidity, and sympathetic and parasympathetic modulation indicate low risk of morbidity. The low risk of morbidity could be the biased production of Ang1-7 in the heart and circulation; however, the altered response of AT1R in the TGM'(rTon) remains to be elucidated, as well aswhether that signaling is pro-protection or pro-pathology.
- 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.
- Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats(2013) FUENTE, Raquel N. de La; RODRIGUES, Bruno; MORAES-SILVA, Ivana C.; SOUZA, Leandro E.; SIRVENTE, Raquel; MOSTARDA, Cristiano; ANGELIS, Katia De; SOARES, Pedro P.; LACCHINI, Silvia; CONSOLIM-COLOMBO, Fernanda; IRIGOYEN, Maria-Claudia1. In the present study we evaluated the effects of shortterm pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats. 2. Male Wistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine-treated groups. Pyridostigmine was administered in the drinking water, starting immediately after MI or sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly by LV catheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment. 3. Pyridostigmine prevented the impairment of + dP/dT and reduced the MI area in infarcted + pyridostigmine compared with infarcted rats (7 +/- 3% vs 17 +/- 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 +/- 3 vs 94 +/- 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 +/- 0.2 vs 2.5 +/- 0.2 b. p. m./mmHg, respectively) and bradycardic (-0.42 +/- 0.01 vs -1.9 +/- 0.1 b. p. m./mmHg) responses, and reduced the low frequency/high frequency ratio of HRV (0.81 +/- 0.11 vs 0.24 +/- 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats. 4. In conclusion, the data suggest that short-term pyridostigmine treatment started early after MI can improve BRS, HRV and parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance after MI.
- Klotho deficiency aggravates sepsis-related multiple organ dysfunction(2019) JORGE, Lecticia B.; COELHO, Fernanda O.; SANCHES, Talita R.; MALHEIROS, Denise M. A. C.; SOUZA, Leandro Ezaquiel de; SANTOS, Fernando dos; LIMA, Larissa de Sa; SCAVONE, Cristoforo; IRIGOYEN, Maria; KURO-O, Makoto; ANDRADE, LuciaSepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP-Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-KB activation. It is noteworthy that CLP-Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprussidc, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction. Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.
- (Pro)renin receptor expression in myocardial infarction in transgenic mice expressing rat tonin(2018) RIBEIRO, Amanda A.; AMORIM, Rebeca Padrao; PALOMINO, Zaira J.; LIMA, Mercia de Paula; MORAES-SILVA, Ivana Cinthya; SOUZA, Leandro Ezequiel; PESQUERO, Jorge Luiz; IRIGOYEN, Maria Claudia; CASARINI, Dulce E.The (pro)renin receptor [(P)RR] has been implicated as a renin/prorenin receptor, and plays a role in local renin angiotensin system activation. Our goal was to investigate whether a transgenic mouse that expresses rat tonin [TGM'(rTon)] can regulate (P)RR mRNA levels. Control (C) and TGM'(rTon) animals were subdivided into the C sham, C MI, TGM'(rTon) sham, and TGM'(rTon) MI groups. The levels of tonin, (P)RR, and renin were determined using RT-PCR mRNA. Tonin activity as determined by RIE was significantly increased in the TGM'(rTon) sham group as compared to the C sham group in the atrium (AT) and right ventricle (RV), respectively. In most mice, tonin mRNA levels were significantly reduced compared to those in the TGM'(rTon) sham group in the atria. In this structure, the (P)RR mRNA levels were statistically significantly reduced in the TGM'(rTon) sham and TGM'(rTon) MI groups compared to the control groups. However, the (P)RR mRNA values were significantly increased when we compared the TGM'(rTon) MI vs TGM'(rTon) sham groups. In the RV, the renin mRNA levels in the TGM'(rTon) sham group were significantly reduced compared to the C sham group. Tonin overexpression may act in the regulation of (P)RR mRNA levels during MI.