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
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
conferenceObject Impact of sympathectomy upon myocardium(2019) PESSOA, F. Fernanda; JORDAO, M. R.; FONSECA, K. C. B.; ZANONI, F.; SALEMI, V. M. C.; RIBEIRO, O. N.; SOUZA, L. E.; FERNANDES, F.; IRIGOYEN, M. C.; MOREIRA, L. F. P.; MADY, C.; RAMIRES, F. J. A.- 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.
- 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.
- Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice(2019) SOUZA-NETO, Fernando Pedro de; SILVA, Mario de Morais e; SANTUCHI, Melissa de Carvalho; ALCANTARA-LEONIDIO, Thais Cristina de; MOTTA-SANTOS, Daisy; OLIVEIRA, Aline Cristina; MELO, Marcos Barrouin; CANTA, Giovanni Naves; SOUZA, Leandro Eziquiel de; IRIGOYEN, Maria Claudia Costa; CAMPAGNOLE-SANTOS, Maria Jose; GUATIMOSIM, Silvia; SANTOS, Robson Augusto Souza; SILVA, Rafaela Fernandes daAims: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine (Ala(1)-angiotensin-(1-7)) is a new biologically active peptide from the RAS, interacting withMas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. In the present study, we investigated the effects of alamandine on ascending aorta remodelling after transverse aortic constriction (TAC) in mice. Methods and results: C57BL/6J male mice were divided into the following groups: Sham (sham-operated), TAC (operated) and TAC+ALA (operated and treated with alamandine-HP beta CD (2-Hydroxypropyl-beta-cyclodextrin), 30 mu g/kg/day, by gavage). Oral administration of alamandine for 14 days attenuated arterial remodelling by decreasing ascending aorta media layer thickness and the cells density in the adventitia induced by TAC. Alamandine administration attenuated ascending aorta fibrosis induced by TAC, through a reduction in the following parameters; total collagen deposition, expression collagen III and transforming growth factor-beta (TGF-beta) transcripts, matrix metalloproteinases (MMPs) activity and vascular expression of MMP-2. Importantly, alamandine decreased vascular expression of proinflammatory genes as CCL2, tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), and was able to increase expression of MRC1 and FIZZ1, pro-resolution markers, after TAC surgery. Conclusion: Alamandine treatment attenuates vascular remodelling after TAC, at least in part, through anti-fibrotic and anti-inflammatory effects. Hence, this work opens new avenues for the use of this heptapeptide also as a therapeutic target for vascular disease.
- Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice(2019) LIMA, Rariane Silva de; SILVA, Juliane Cristina de Souza; LIMA, Cintia Taniguti; SOUZA, Leandro Ezequiel de; SILVA, Maikon Barbosa da; BALADI, Marina Gazzano; IRIGOYEN, Maria Claudia; LACCHINI, SilviaAngiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-, TGF-, iNOS, CD45, and -actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1- and TGF- expression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting to -actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.