LEONARDO JENSEN SOCAS
Projetos de Pesquisa
Unidades Organizacionais
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- 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.
- Pyridostigmine Bromide: Autonomic Nervous System Modulation Reduces Adipose and Splenic Tissue Weight in Leptin-Deficienty Ob/Ob Mice(2020) RIBEIRO, Amanda; SANTOS, Fernando dos; ARNOLD, Alexandre; BARBOSA, Maikon; JENSEN, Leonardo; IRIGOYEN, Maria Costa
- Cardioprotection Conferred by Sitagliptin Is Associated with Reduced Cardiac Angiotensin II/Angiotensin-(1-7) Balance in Experimental Chronic Kidney Disease(2019) BERALDO, Juliana Isa; BENETTI, Acaris; BORGES-JUNIOR, Flavio Araujo; ARRUDA-JUNIOR, Daniel F.; MARTINS, Flavia Leticia; JENSEN, Leonardo; DARIOLLI, Rafael; SHIMIZU, Maria Heloisa; SEGURO, Antonio C.; LUCHI, Weverton M.; GIRARDI, Adriana C. C.Dipeptidyl peptidase IV (DPPIV) inhibitors are antidiabetic agents that exert renoprotective actions independently of glucose lowering. Cardiac dysfunction is one of the main outcomes of chronic kidney disease (CKD); however, the effects of DPPIV inhibition on cardiac impairment during CKD progression remain elusive. This study investigated whether DPPIV inhibition mitigates cardiac dysfunction and remodeling in rats with a 5/6 renal ablation and evaluated if these effects are associated with changes in the cardiac renin-angiotensin system (RAS). To this end, male Wistar rats underwent a 5/6 nephrectomy (Nx) or sham operation, followed by an 8-week treatment period with the DPPIV inhibitor sitagliptin (IDPPIV) or vehicle. Nx rats had lower glomerular filtration rate, overt albuminuria and higher blood pressure compared to sham rats, whereas CKD progression was attenuated in Nx + IDPPIV rats. Additionally, Nx rats exhibited cardiac hypertrophy and fibrosis, which were associated with higher cardiac DPPIV activity and expression. The sitagliptin treatment prevented cardiac fibrosis and mitigated cardiac hypertrophy. The isovolumic relaxation time (IRVT) was higher in Nx than in sham rats, which was suggestive of CKD-associated-diastolic dysfunction. Sitagliptin significantly attenuated the increase in IRVT. Levels of angiotensin II (Ang II) in the heart tissue from Nx rats were higher while those of angiotensin-(1-7) Ang-(1-7) were lower than that in sham rats. This cardiac hormonal imbalance was completely prevented by sitagliptin. Collectively, these results suggest that DPPIV inhibition may delay the onset of cardiovascular impairment in CKD. Furthermore, these findings strengthen the hypothesis that a crosstalk between DPPIV and the renin-angiotensin system plays a role in the pathophysiology of cardiorenal syndromes.
- A Sodium Oxalate-Rich Diet Induces Chronic Kidney Disease and Cardiac Dysfunction in Rats(2021) CRESTANI, Thayane; CRAJOINAS, Renato O.; JENSEN, Leonardo; DIMA, Leno L.; BURDEYRON, Perrine; HAUET, Thierry; GIRAUD, Sebastien; STEICHEN, ClaraChronic kidney disease (CKD) is a worldwide public health issue affecting 14% of the general population. However, research focusing on CKD mechanisms/treatment is limited because of a lack of animal models recapitulating the disease physiopathology, including its complications. We analyzed the effects of a three-week diet rich in sodium oxalate (OXA diet) on rats and showed that, compared to controls, rats developed a stable CKD with a 60% reduction in glomerular filtration rate, elevated blood urea levels and proteinuria. Histological analyses revealed massive cortical disorganization, tubular atrophy and fibrosis. Males and females were sensitive to the OXA diet, but decreasing the diet period to one week led to GFR significance but not stable diminution. Rats treated with the OXA diet also displayed classical CKD complications such as elevated blood pressure and reduced hematocrit. Functional cardiac analyses revealed that the OXA diet triggered significant cardiac dysfunction. Altogether, our results showed the feasibility of using a convenient and non-invasive strategy to induce CKD and its classical systemic complications in rats. This model, which avoids kidney mass loss or acute toxicity, has strong potential for research into CKD mechanisms and novel therapies, which could protect and postpone the use of dialysis or transplantation.
conferenceObject Dipeptidyl peptidase IV inhibition ameliorates cardiorenal function in experimental heart failure(2014) ARRUDA-JUNIOR, Daniel; SOCAS, Leonardo; DARIOLLI, Rafael; ANTONIO, Ednei; TUCCI, Paulo; SANTOS, Leonardo dos; GIRARDI, Adriana