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

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  • article 23 Citação(ões) na Scopus
    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.
  • article 21 Citação(ões) na Scopus
    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, Lucia
    Sepsis-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.
  • article 28 Citação(ões) na Scopus
    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 da
    Aims: 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.