LEONARDO JENSEN SOCAS
Projetos de Pesquisa
Unidades Organizacionais
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- 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
conferenceObject Cardiac Hypertrophy and Altered Glycolytic Metabolism are Reversed in an Aortic Constriction Mice Model(2019) JENSEN, Leonardo; SILVA, Amanda; FARIA, Daniele; VENTURINI, Gabriela; PEREIRA, Alexandre; BUCHPIGUEL, Carlos Alberto; IRIGOYEN, Maria Claudia C.- THE EFFECTS OF PYRIDOSTIGMINE BROMIDE ON AUTONOMIC, HEMODYNAMIC AND METABOLIC PARAMETERS IN FEMALE OVARIECTOMIZED C57BL/6 MICE(2018) RIBEIRO, Amanda; SILVA, Maikon; ARNOLD, Alexandre Jose; JENSEN, Leonardo; SANTOS, Fernando; IRIGOYEN, Maria-Claudia
conferenceObject Reversal of Cardiac Remodeling After Surgical Intervention Leads to Distinct Cardiac Function Outcomes.(2017) JENSEN, Leonardo; SILVA, Amanda Almeida; OLIVEIRA, Nataly Cunha; SOUZA, Leandro Eziquiel de; IRIGOYEN, Maria Claudio Costa- Wharton's jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation(2020) CAPCHA, Jose Manuel Condor; RODRIGUES, Camila Eleuterio; MOREIRA, Roberto de Souza; SILVEIRA, Marcelo Duarte; DOURADO, Paulo; SANTOS, Fernando dos; IRIGOYEN, Maria Claudia; JENSEN, Leonardo; GARNICA, Margoth Ramos; NORONHA, Irene L.; ANDRADE, Lucia; GOMES, Samirah AbreuSepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton's jellyderived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by alpha 7-nicotinic acetylcholine receptors (alpha 7nAChRs). which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CL.P+WJ-MSCs (1 x 10(6) cells, at 6 h post-CLP); and CLP+methyllycaconifine (MLA)+WJ-MSCs (5 mg/kg body wt, at 53 h post-CLP, and 1 x 10(6) cells, at 6 h post-CLP. respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective alpha 7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated alpha 7nAChR expression, as well as reduced the phospho-STAT3-tototal STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.
- The miRNA-143-3p-Sox6-Myh7 pathway is altered in obesogenic diet-induced cardiac hypertrophy(2022) SILVA, Tabatha de Oliveira; LINO, Caroline A.; MIRANDA, Juliane B.; BALBINO-SILVA, Camila S.; LUNARDON, Guilherme; LIMA, Vanessa M.; JENSEN, Leonardo; DONATO JR., Jose; IRIGOYEN, Maria Claudia; BARRETO-CHAVES, Maria Luiza M.; DINIZ, Gabriela P.New Findings What is the central question of this study? What is the effect of an obesogenic diet on the expression of microRNAs (miRNAs) involved in cardiac hypertrophy in female mice? What is the main finding and its importance? Female mice fed an obesogenic diet exhibited cardiac hypertrophy associated with increased levels of miRNA-143-3p, decreased mRNA levels of Sox6 and increased mRNA levels of Myh7. Inhibition of miRNA-143-3p increased Sox6 mRNA levels and reduced Myh7 expression in cardiomyocytes, and prevented angiotensin II-induced cardiomyocyte hypertrophy. The results indicate that the miRNA-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy. Obesity induces cardiometabolic disorders associated with a high risk of mortality. We have previously shown that the microRNA (miRNA) expression profile is changed in obesity-induced cardiac hypertrophy in male mice. Here, we investigated the effect of an obesogenic diet on the expression of miRNAs involved in cardiac hypertrophy in female mice. Female mice fed an obesogenic diet displayed an increased body weight gain, glucose intolerance, insulin resistance and dyslipidaemia. In addition, obese female mice exhibited cardiac hypertrophy associated with increased levels of several miRNAs, including miR-143-3p. Bioinformatic analysis identified Sox6, regulator of Myh7 gene transcription, as a predicted target of miR-143-3p. Female mice fed an obesogenic diet exhibited decreased mRNA levels of Sox6 and increased expression of Myh7 in the heart. Loss-of-function studies in cardiomyocytes revealed that inhibition of miR-143-3p increased Sox6 mRNA levels and reduced Myh7 expression. Collectively, our results indicate that obesity-associated cardiac hypertrophy in female mice is accompanied by alterations in diverse miRNAs, and suggest that the miR-143-3p-Sox6-Myh7 pathway may play a key role in obesity-induced cardiac hypertrophy.
- Set7 Deletion Prevents Glucose Intolerance and Improves the Recovery of Cardiac Function after Ischemia and Reperfusion in Obese Female Mice(2022) MIRANDA, J. B.; LUNARDON, G.; LIMA, V. M.; SILVA, T. de Oliveira; LINO, C. A.; JENSEN, L.; IRIGOYEN, M. C.; SILVA, I. B. da; LU, Y. W.; LIU, J.; JúNIOR, J. D.; BARRETO-CHAVES, M. L. M.; WANG, D.-Z.; DINIZ, G. P.Background/Aims: An obesogenic diet (high fat and sugar, low fiber) is associated with an increased risk for metabolic and cardiovascular disorders. Previous studies have demonstrated that epigenetic changes can modify gene transcription and protein function, playing a key role in the development of several diseases. The methyltransferase Set7 methylates histone and non-histone proteins, influencing diverse biological and pathological processes. However, the functional role of Set7 in obesity-associated metabolic and cardiovascular complications is unknown. Methods: Wild type and Set7 knockout female mice were fed a normal diet or an obesogenic diet for 12 weeks. Body weight gain and glucose tolerance were measured. The 3T3-L1 cells were used to determine the role of Set7 in white adipogenic differentiation. Cardiac morphology and function were evaluated by histology and echocardiography. An ex vivo Langendorff perfusion system was used to model cardiac ischemia/reperfusion (I/R). Results: Here, we report that Set7 protein levels were enhanced in the heart and perigonadal adipose tissue (PAT) of female mice fed an obesogenic diet. Significantly, loss of Set7 prevented obesogenic diet-induced glucose intolerance in female mice although it did not affect the obesogenic diet-induced increase in body weight gain and adiposity in these animals, nor did Set7 inhibition change white adipogenic differentiation in vitro. In addition, loss of Set7 prevented the compromised cardiac functional recovery following ischemia and reperfusion (I/R) injury in obesogenic diet-fed female mice; however, deletion of Set7 did not influence obesogenic diet-induced cardiac hypertrophy nor the hemodynamic and echocardiographic parameters. Conclusion: These data indicate that Set7 plays a key role in obesogenic dietinduced glucose intolerance and compromised myocardial functional recovery after I/R in obese female mice. © 2022 Published The Author(s)