JOEL CLAUDIO HEIMANN
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/16 - Laboratório de Fisiopatologia Renal, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject Effect of an angiotensin II type 2 receptor agonist on myocardial hypertrophy and fibrosis induced by high salt diet(2017) DOPONA, Ellen Priscila Brito; ROCHA, Veronica Favoni; OLIVEIRA, Ivone Braga de; FURUKAWA, Luzia Naoko Shinohara; HEIMANN, Joel Claudio- A novel peptide that improves metabolic parameters without adverse central nervous system effects(2017) RECKZIEGEL, Patricia; FESTUCCIA, William T.; BRITTO, Luiz R. G.; JANG, Karen L. Lopes; ROMAO, Carolina M.; HEIMANN, Joel C.; FOGACA, Manoela V.; RODRIGUES, Naielly S.; SILVA, Nicole R.; GUIMARAES, Francisco S.; EICHLER, Rosangela A. S.; GUPTA, Achla; GOMES, Ivone; DEVI, Lakshmi A.; HEIMANN, Andrea S.; FERRO, Emer S.Intracellular peptides generated by limited proteolysis are likely to function inside and outside cells and could represent new possibilities for drug development. Here, we used several conformational-sensitive antibodies targeting G-protein coupled receptors to screen for novel pharmacological active peptides. We find that one of these peptides, DITADDEPLT activates cannabinoid type 1 receptors. Single amino acid modifications identified a novel peptide, DIIADDEPLT (Pep19), with slightly better inverse agonist activity at cannabinoid type 1 receptors. Pep19 induced uncoupling protein 1 expression in both white adipose tissue and 3T3-L1 differentiated adipocytes; in the latter, Pep19 activates pERK1/2 and AKT signaling pathways. Uncoupling protein 1 expression induced by Pep19 in 3T3-L1 differentiated adipocytes is blocked by AM251, a cannabinoid type 1 receptors antagonist. Oral administration of Pep19 into diet-induced obese Wistar rats significantly reduces adiposity index, whole body weight, glucose, triacylglycerol, cholesterol and blood pressure, without altering heart rate; changes in the number and size of adipocytes were also observed. Pep19 has no central nervous system effects as suggested by the lack of brain c-Fos expression, cell toxicity, induction of the cannabinoid tetrad, depressive-and anxiety-like behaviors. Therefore, Pep19 has several advantages over previously identified peripherally active cannabinoid compounds, and could have clinical applications.
- Low-sodium diet induces atherogenesis regardless of lowering blood pressure in hypertensive hyperlipidemic mice(2017) FUSCO, Fernanda B.; GOMES, Diego J.; BISPO, Kely C. S.; TOLEDO, Veronica P.; BARBEIRO, Denise F.; CAPELOZZI, Vera L.; FURUKAWA, Luzia N. S.; VELOSA, Ana P. P.; TEODORO, Walcy R.; HEIMANN, Joel C.; QUINTAO, Eder C. R.; PASSARELLI, Marisa; NAKANDAKARE, Edna R.; CATANOZI, SergioThis study investigated the influence of sodium restriction and antihypertensive drugs on atherogenesis utilizing hypertensive (H) low-density lipoprotein-receptor knockout mice treated or not with losartan (Los) or hydralazine (Hyd) and fed low-sodium (LS) or normal-sodium (NS) chow. Despite reducing the blood pressure (BP) of H-LS mice, the LS diet caused arterial lipid infiltration due to increased plasma total cholesterol (TC) and triglycerides (TG). Los and Hyd reduced the BP of H-LS mice, and Los effectively prevented arterial injury, likely by reducing plasma TG and nonesterified fatty acids. Aortic lipid infiltration was lower in Los-treated H-LS mice (H-LS+Los) than in normotensive (N)-LS and H-LS mice. Aortic angiotensin II type 1 (AT1) receptor content was greater in H-NS than H-LS mice and in H-LS+Hyd than H-LS+Los mice. Carboxymethyl-lysine (CML) and receptor for advanced glycation end products (RAGE) immunostaining was greater in H-LS than H-NS mice. CML and RAGE levels were lower in LS animals treated with antihypertensive drugs, and Hyd enhanced the AT1 receptor level. Hyd also increased the gene expression of F4/80 but not tumor necrosis factor-a, interleukin (IL)-1 beta, IL-6, IL-10, intercellular adhesion molecule-1 or cluster of differentiation 66. The novelty of the current study is that in a murine model of simultaneous hypertension and hyperlipidemia, the pleiotropic effect of chronic, severe sodium restriction elicited aortic damage even with reduced BP. These negative effects on the arterial wall were reduced by AT1 receptor antagonism, demonstrating the influence of angiotensin II in atherogenesis induced by a severely LS diet.
- Exposure to fine particulate matter in the air alters placental structure and the renin-angiotensin system(2017) SOTO, Sonia de Fatima; MELO, Juliana Oliveira de; MARCHESI, Guilherme D'Aprile; LOPES, Karen Lucasechi; VERAS, Mariana Matera; OLIVEIRA, Ivone Braga de; SOUZA, Regiane Machado de; CASTRO, Isac de; FURUKAWA, Luzia Naoko Shinohara; SALDIVA, Paulo Hilario Nascimento; HEIMANN, Joel C.Transforming growth factor beta 1 (TGF beta 1), the uteroplacental renin-angiotensin system (RAS) and vascular endothelial growth factor A (VEGF-A) participate in the placentation process. The aim of this study was to investigate the effects of exposure to pollutants on the placenta. Methods Female Wistar rats were exposed to filtered air (F) or to concentrated fine particulate matter (P) for 15 days. After mating, the rats were divided into four groups and again exposed to F or P (FF, FP, PF, PP) beginning on day 6 of pregnancy. At embryonic day 19, the placenta was collected. The placental structure, the protein and gene expression of TGF beta 1, VEGF-A, and its receptor Flk-1 and RAS were evaluated by indirect ELISA and quantitative real-time PCR. Results Exposure to P decreased the placental mass, size, and surface area as well as the TGF beta 1, VEGF-A and Flk-1 content. In the maternal portion of the placenta, angiotensin II (AngII) and its receptors AT(1) (AT(1)R) and AT(2) (AT(2)R) were decreased in the PF and PP groups. In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT(2)R in the PF and PP groups were decreased, but AT(1)R was increased in the FP group. VEGF-A gene expression was lower in the PP group than in the FF group. Conclusions Exposure to pollutants before and/or during pregnancy alters some characteristics of the placenta, indicating a possible impairment of trophoblast invasion and placental angiogenesis with possible consequences for the maternal-fetal interaction, such as a limitation of fetal nutrition and growth.
- The effects of individually ventilated cages on the respiratory systems of male and female Wistar rats from birth until adulthood(2017) MARCHESI, Guilherme DAprile; SOTO, Sonia de Fatima; CASTRO, Isac de; RODRIGUES, Thiago Guimaraes; MORIYA, Henrique Takachi; ALMEIDA, Francine Maria de; PAZETTI, Rogerio; HEIMANN, Joel Claudio; FURUKAWA, Luzia Naoko ShinoharaOBJECTIVE: To evaluate the respiratory systems of male and female rats maintained in individually ventilated cages (IVCs) from birth until adulthood. METHODS : Female Wistar rats were housed in individually ventilated cages or conventional cages (CCs) and mated with male Wistar rats. After birth and weaning, the male offspring were separated from the females and kept in cages of the same type until 12 weeks of age. RESULTS: The level of food consumption was lower in male offspring (IVC=171.7 +/- 9; CC=193.1 +/- 20) than in female offspring (IVC=100.6 +/- 7; CC=123.4 +/- 0.4), whereas the water intake was higher in female offspring (IVC=149.8 +/- 11; CC=99.2 +/- 0) than in male offspring (IVC=302.5 +/- 25; CC=249.7 +/- 22) at 11 weeks of age when housed in IVCs. The cage temperature was higher in individually ventilated cages than in conventional cages for both male (IVCs=25.9 +/- 0.5; CCs=22.95 +/- 0.3) and female (IVCs=26.2 +/- 0.3; CCs=23.1 +/- 0.3) offspring. The respiratory resistance (IVC=68.8 +/- 2.8; CC=50.6 +/- 3.0) and elastance (IVC=42.0 +/- 3.9; CC=32.4 +/- 2.0) at 300 mm/kg were higher in the female offspring housed in ventilated cages. The ciliary beat values were lower in both the male (IVCs=13.4 +/- 0.2; CC=15 +/- 0.4) and female (IVC=13.5 +/- 0.4; CC=15.9 +/- 0.6) offspring housed in individually ventilated cages than in those housed in conventional cages. The total cell (IVC=117.5 +/- 9.7; CC=285.0 +/- 22.8), neutrophil (IVC=13.1 +/- 4.8; CC=75.6 +/- 4.1) and macrophage (IVC=95.2 +/- 11.8; CC=170.0 +/- 18.8) counts in the bronchoalveolar lavage fluid were lower in the female offspring housed in individually ventilated cages than in those housed in conventional cages. CONCLUSIONS : The environmental conditions that exist in individually ventilated cages should be considered when interpreting the results of studies involving laboratory animals. In this study, we observed gender dimorphism in both the water consumption and respiratory mechanics of rats kept in ventilated cages.