ELIA TAMASO ESPIN GARCIA CALZOLARI

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Departamento de Patologia, Faculdade de Medicina - Docente
LIM/59 - Laboratório de Biologia Celular, Hospital das Clínicas, Faculdade de Medicina

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  • conferenceObject
    ELEVATED ROS LEVELS AND DNA FRAGMENTATION IN SPERM FROM CONVALESCENT MEN IN SARS-COV-2 INFECTION
    (2022) HALLAK, Jorge; BERNARDES, Felipe; TEIXEIRA, Thiago Afonso Carvalho Celestino; SALDIVA, Paulo Hilario Nascimento; KALLAS, Esper Georges; CALDINI, Elia Tamaso Espin Garcia; DUARTE NETO, Amaro Nunes; FAQUINETI, Heloisa; JESUS, Vinicius Luiz Menezes; GUTIERREZ, Raul Segundo Sanchez; DREVET, Joel R.
  • article 23 Citação(ões) na Scopus
    Baroreflex Sensitivity Impairment Is Associated With Cardiac Diastolic Dysfunction in Rats
    (2011) MOSTARDA, Cristiano; MORAES-SILVA, Ivana Cinthya; MOREIRA, Edson Dias; MEDEIROS, Alessandra; PIRATELLO, Aline Cristina; CONSOLIM-COLOMBO, Fernanda Marciano; CALDINI, Elia Garcia; BRUM, Patricia Chakur; KRIEGER, Eduardo Moacyr; IRIGOYEN, Maria Claudia
    Background: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morpho-functional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). Methods and Results: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 +/- 0.07 ms vs 1.78 +/- 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 +/- 1.5 mm Hg vs 5.3 +/- 0.2 mm Hg and 7,422 +/- 201 vs 4,999 +/- 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. Conclusions: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors. (J Cardiac Fail 2011;17:519-525)
  • article 45 Citação(ões) na Scopus
    Dietary interesterified fat enriched with palmitic acid induces atherosclerosis by impairing macrophage cholesterol efflux and eliciting inflammation
    (2016) AFONSO, Milessa Silva; LAVRADOR, Maria Silvia Ferrari; KOIKE, Marcia Kiyomi; CINTRA, Dennys Esper; FERREIRA, Fabiana Dias; NUNES, Valeria Sutti; CASTILHO, Gabriela; GIOIELLI, Luiz Antonio; BOMBO, Renata Paula; CATANOZI, Sergio; CALDINI, Elia Garcia; DAMACENO-RODRIGUES, Nilsa Regina; PASSARELLI, Marisa; NAKANDAKARE, Edna Regina; LOTTENBERG, Ana Maria
    Interesterified fats are currently being used to replace trans fatty acids. However, their impact on biological pathways involved in the atherosclerosis development was not investigated. Weaning male LDLr-KO mice were fed for 16 weeks on a high-fat diet (40% energy as fat) containing polyunsaturated (PUFA), TRANS, palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR) or stearic interesterified (STEAR INTER). Plasma lipids, lipoprotein profile, arterial lesion area, macrophage infiltration, collagen content and inflammatory response modulation were determined. Macrophage cholesterol efflux and the arterial expression of cholesterol uptake and efflux receptors were also performed. The interesterification process did not alter plasma lipid concentrations. Although PALM INTER did not increase plasma cholesterol concentration as much as TRANS, the cholesterol enrichment in the LDL particle was similar in both groups. Moreover, PALM INTER induced the highest IL-1 beta, MCP-1 and IL-6 secretion from peritoneal macrophages as compared to others. This inflammatory response elicited by PALM INTER was confirmed in arterial wall, as compared to PALM. These deleterious effects of PALM INTER culminate in higher atherosclerotic lesion, macrophage infiltration and collagen content than PALM, STEAR, STEAR INTER and PUFA. These events can partially be attributed to a macrophage cholesterol accumulation, promoted by apoAl and HDL2-mediated cholesterol efflux impairment and increased Olr-1 and decreased Abca1 and Nr1h3 expressions in the arterial wall. Interesterified fats containing palmitic acid induce atherosclerosis development by promoting cholesterol accumulation in LDL particles and macrophagic cells, activating the inflammatory process in LDLr-KO mice.
  • article 24 Citação(ões) na Scopus
    Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling
    (2016) PEREIRA, Paulo Rogerio; OLIVEIRA-JUNIOR, Manoel Carneiro; MACKENZIE, Breanne; CHIOVATTO, Jaime Eduardo Davino; MATOS, Yves; GREIFFO, Flavia Regina; RIGONATO-OLIVEIRA, Nicole Cristine; BRUGEMMAN, Thayse Regina; DELLE, Humberto; IDZKO, Marco; ALBERTINI, Regiane; OLIVEIRA, Ana Paula Ligeiro; DAMACENO-RODRIGUES, Nilsa Regina; CALDINI, Elia Garcia; FERNANDEZ, Isis Ensil; CASTRO-FARIA-NETO, Hugo Caire; DOLHNIKOFF, Marisa; EICKELBERG, Oliver; VIEIRA, Rodolfo Paula
    Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Methods: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI.kg(-1)) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min.d(-1), 5 d.wk(-1) for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1A, IL-6, CXCL1/KC, IL-10, tumor necrosis factor alpha, and transforming growth factor A levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. Results: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1A (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor > (P < 0.001), and transforming growth factor A (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. Conclusions: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.
  • article 16 Citação(ões) na Scopus
    Baroreflex Impairment Precedes Cardiometabolic Dysfunction in an Experimental Model of Metabolic Syndrome: Role of Inflammation and Oxidative Stress
    (2018) BERNARDES, Nathalia; DIAS, Danielle da Silva; STOYELL-CONTI, Filipe Fernandes; BRITO-MONZANI, Janaina de Oliveira; MALFITANO, Christiane; CALDINI, Elia Garcia; ULLOA, Luis; LLESUY, Susana Francisca; IRIGOYEN, Maria-Claudia; ANGELIS, Katia De
    This study analyzes whether autonomic dysfunction precedes cardiometabolic alterations in spontaneously hypertensive rats (SHR) with fructose overload. Animals were randomly distributed into three groups: control, hypertensive and hypertensive with fructose overload. Fructose overload (100 g/L) was initiated at 30 days old, and the animals (n = 6/group/time) were evaluated after 7,15, 30 and 60 days of fructose consumption. Fructose consumption reduced baroreflex sensitivity by day 7, and still induced a progressive reduction in baroreflex sensitivity over the time. Fructose consumption also increased TNF alpha and IL-6 levels in the adipose tissue and IL-1 beta(3 levels in the spleen at days 15 and 30. Fructose consumption also reduced plasmatic nitrites (day 15 and 30) and superoxide dismutase activity (day 15 and 60), but increased hydrogen peroxide (day 30 and 60), lipid peroxidation and protein oxidation (day 60). Fructose consumption increased arterial pressure at day 30 (8%) and 60 (11%). Fructose consumption also induced a late insulin resistance at day 60, but did not affect glucose levels. In conclusion, the results show that baroreflex sensitivity impairment precedes inflammatory and oxidative stress disorders, probably by inducing hemodynamic and metabolic dysfunctions observed in metabolic syndrome.
  • article 11 Citação(ões) na Scopus
    ENDOTOXEMIC MYOCARDIAL DYSFUNCTION: SUBENDOCARDIAL COLLAGEN DEPOSITION RELATED TO CORONARY DRIVING PRESSURE
    (2014) SORIANO, Francisco Garcia; GUIDO, Maria Carolina; BARBEIRO, Hermes Vieira; CALDINI, Elia Garcia; LORIGADOS, Clara Batista; NOGUEIRA, Antonio Carlos
    Sepsis impairs the autoregulation of myocardial microcirculatory blood flow, but whether this impairment is correlated with myocardial remodeling is unknown. This study investigated the role of coronary driving pressure (CDP) as a determinant of microcirculatory blood flow and myocardial fibrosis in endotoxemia and sepsis. The study is composed of two parts: a prospective experimental study and an observational clinical study. The experimental study was performed on male Wistar rats weighing 300 to 320 g. Endotoxemia was induced in rats by lipopolysaccharide (LPS) injection (10 mg.kg(-1) intraperitoneally). Hemodynamic evaluation was performed 1.5 to 24 h after LPS injection by measuring the mean arterial pressure, CDP, left ventricular end-diastolic pressure, dP/dtmax, and dP/dtmin. Microspheres were also infused into the left ventricle to measure myocardial blood flow, and myocardial tissue was histologically assessed to analyze collagen deposition. The CDP, mean arterial pressure, and myocardial blood flow were reduced by 55%, 30%, and 70%, respectively, in rats 1.5 h after LPS injection compared with phosphate buffer saline injection (P < 0.05). The CDP was significantly correlated with subendocardial blood flow (r = 0.73) and fibrosis (r = 0.8). Left ventricular function was significantly impaired in the LPS-treated rats, as demonstrated by dP/dtmax (6,155 +/- 455 vs. 3,746 +/- 406 mmHg.s(-1), baseline vs. LPS; P < 0.05) and dP/dtmin (-5,858 +/- 236 vs. -3,516 +/- 436 mmHg.s(-1), baseline vs. LPS; P < 0.05). The clinical study was performed on 28 patients with septic shock analyzed for CDP. The CDP data and histological slices were collected from septic patients. In addition, the clinical data demonstrated fibrosis and 45% CDP reduction in nonsurvivors compared with survivors. In conclusion, the left ventricular subendocardial blood flow was positively correlated with CDP, and higher CDP was negatively correlated with myocardial collagen deposition. Thus, early reductions in myocardial blood flow and CDP facilitate late myocardial fibrosis in rats and likely in humans.
  • article 3 Citação(ões) na Scopus
    Comparative Morphometric Analysis of 5 Interpositional Arterial Autograft Options for Adult Living Donor Liver Transplantation
    (2014) IMAKUMA, E. S.; BORDINI, A. L.; MILLAN, L. S.; MASSAROLLO, P. C. B.; CALDINI, E. T. E. G.
    In living donor liver transplantation, the right-sided graft presents thin and short vessels, bringing forward a more difficult anastomosis. In these cases, an interpositional arterial autograft can be used to favor the performance of the arterial anastomosis, making the procedure easier and avoiding surgical complications. Objective. We compared the inferior mesenteric artery (IMA), the splenic artery (SA), the inferior epigastric artery (TEA), the descending branch of the lateral circumflex femoral artery (LCFA), and the proper hepatic artery (PHA) as options for interpositional autograft in living donor liver transplantation. Method. Segments of at least 3 cm of all 5 arteries were harvested from 16 fresh adult cadavers from both genders through standardized dissection. The analyzed measures were proximal and distal diameter and length. The proximal diameter of the RHA and the distal diameter of the SA, IMA, IEA and the LCFA were compared to the distal diameter of the RHA. The proximal and distal diameters of the SA, TEA and LCFA were compared to study caliber gain of each artery. Results. All arteries except the IMA showed statistical significant difference in relation to the RHA in terms of diameter. Regarding caliber gain, the arteries demonstrated statistical significant difference. All the harvested arteries except PHA were 3 cm in length. Conclusion. The IMA demonstrated the best compatibility with the RI-TA in terms of diameter and showed sufficient length to be employed as interpositional graft. The PHA, the SA, the TEA and the LCFA presented statistically significant different diameters when compared to the RHA. Among these vessels, only the PHA did not show sufficient mean length.
  • article 10 Citação(ões) na Scopus
    SMALL INTERFERING RNA TARGETING FOCAL ADHESION KINASE PREVENTS CARDIAC DYSFUNCTION IN ENDOTOXEMIA
    (2012) GUIDO, Maria C.; CLEMENTE, Carolina F.; MORETTI, Ana I.; BARBEIRO, Hermes V.; DEBBAS, Victor; CALDINI, Elia G.; FRANCHINI, Kleber G.; SORIANO, Francisco G.
    Sepsis and septic shock are associated with cardiac depression. Cardiovascular instability is a major cause of death in patients with sepsis. Focal adhesion kinase (FAK) is a potential mediator of cardiomyocyte responses to oxidative and mechanical stress. Myocardial collagen deposition can affect cardiac compliance and contractility. The aim of the present study was to determine whether the silencing of FAK is protective against endotoxemia-induced alterations of cardiac structure and function. In male Wistar rats, endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (10 mg/kg). Cardiac morphometry and function were studied in vivo by left ventricular catheterization and histology. Intravenous injection of small interfering RNA targeting FAK was used to silence myocardial expression of the kinase. The hearts of lipopolysaccharide-injected rats showed collagen deposition, increased matrix metalloproteinase 2 activity, and myocyte hypertrophy, as well as reduced 24-h +dP/dt and -dP/dt, together with hypotension, increased left ventricular end-diastolic pressure, and elevated levels of FAK (phosphorylated and unphosphorylated). Focal adhesion kinase silencing reduced the expression and activation of the kinase in cardiac tissue, as well as protecting against the increased collagen deposition, greater matrix metalloproteinase 2 activity, and reduced cardiac contractility that occur during endotoxemia. In conclusion, FAK is activated in endotoxemia, playing a role in cardiac remodeling and in the impairment of cardiac function. This kinase represents a potential therapeutic target for the protection of cardiac function in patients with sepsis.
  • article 22 Citação(ões) na Scopus
    Effects of Aerobic Exercise on Molecular Aspects of Asthma: Involvement of SOCS-JAK-STAT
    (2019) ALMEIDA-OLIVEIRA, A. R.; AQUINO JR., J. C. J.; ABBASI, A.; SANTOS-DIAS, A.; OLIVEIRA JR., M. C.; ALBERCA-CUSTODIO, R. W.; RIGONATO-OLIVEIRA, N. C.; SALLEY-DIAS, L. P.; DAMACENO-RODRIGUES, N. R.; CALDINI, E. G.; ARANTES-COSTA, F. M.; LIGEIRO-OLIVEIRA, A. P.; BELVISI, M. G.; VIEIRA, R. P.
    Background: Aerobic training (AT) decreases airway inflammation in asthma, but the underlying cellular and molecular mechanisms are not completely understood. Thus, this study evaluated the participation of SOCS-JAK-STAT signaling in the effects of AT on airway inflammation, remodeling and hyperresponsiveness in a model of allergic airway inflammation. Methods: C57Bl/6 mice were divided into Control (Co), Exercise (Ex), HDM (HDM), and HDM+ Exercise (HDM+ Ex). Dermatophagoides pteronyssinus (100ug/mouse) were administered oro-tracheally on days 0, 7, 14, 21, 28, 35, 42 and 49. AT was performed in a treadmill during 4 weeks in moderate intensity, from day 24 until day 52. Results: AT inhibited HDM-induced total cells (p<0.001), eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in BAL, and eosinophils (p<0.01), neutrophils (p<0.01) and lymphocytes (p<0.01) in peribronchial space. AT also reduced BAL levels of IL-4 (p<0.001), IL-5 (p<0.001), IL-13 (p<0.001), CXCL1 (p<0.01), IL-17 (p<0.01), IL-23 (p<0.05), IL-33 (p<0.05), while increased IL-10 (p<0.05). Airway collagen fibers (p<0.01), elastic fibers p<0.01) and mucin (p<0.01) were also reduced by AT. AT also inhibited HDM-induced airway hyperresponsiveness (AHR) to methacholine 6,25mg/ml (p<0.01), 12,5mg/mL (p<0.01), 25mg/mL (p<0.01) and 50mg/mL (p<0.01). Mechanistically, AT reduced the expression of STAT6 (p<0.05), STAT3 (p<0.001), STAT5 (p<0.01) and JAK2 (p<0.001), similarly by peribronchial leukocytes and by airway epithelial cells. SOCS1 expression (p<0.001) was upregulated in leukocytes and in epithelial cells, SOCS2 (p<0.01) was upregulated in leukocytes and SOCS3 down-regulated in leukocytes (p<0.05) and in epithelial cells (p<0.001). Conclusions: AT reduces asthma phenotype involving SOCS-JAK-STAT signaling.
  • article 16 Citação(ões) na Scopus
    Cardiac and pulmonary arterial remodeling after sinoaortic denervation in normotensive rats
    (2012) FLUES, K.; MORAES-SILVA, I. C.; MOSTARDA, C.; SOUZA, P. R. M.; DINIZ, G. P.; MOREIRA, E. D.; PIRATELLO, A. C.; CHAVES, M. L. Barreto; ANGELIS, K. De; SALEMI, Vera Maria Cury; IRIGOYEN, M. C.; CALDINI, E. G.
    Blood pressure variability (BPV) and baroreflex dysfunction may contribute to end-organ damage process. We investigated the effects of baroreceptor deficit (10 weeks after sinoaortic denervation - SAD) on hemodynamic alterations, cardiac and pulmonary remodeling. Cardiac function and morphology of male Wistar intact rats (C) and SAD rats (SAD) (n = 8/group) were assessed by echocardiography and collagen quantification. BP was directly recorded. Ventricular hypertrophy was quantified by the ratio of left ventricular weight (LVW) and right ventricular weight (RVW) to body weight (BW). BPV was quantified in the time and frequency domains. The atrial natriuretic peptide (ANP), alpha-skeletal actin (alpha-skelectal), collagen type I and type III genes mRNA expression were evaluated by RT-PCR. SAD did not change BP, but increased BPV (11 +/- 0.49 vs. 5 +/- 0.3 mm Hg). As expected, baroreflex was reduced in SAD. Pulmonary artery acceleration time was reduced in SAD. In addition, SAD impaired diastolic function in both LV (6.8 +/- 0.26 vs. 5.02 +/- 0.21 mm Hg) and RV (5.1 +/- 0.21 vs. 4.2 +/- 0.12 mm Hg). SAD increased LVW/BW in 9% and RVW/BW in 20%, and augmented total collagen (3.8-fold in LV, 2.7-fold in RV, and 3.35-fold in pulmonary artery). Also, SAD increased type I (similar to 6-fold) and III (similar to 5-fold) collagen gene expression. Denervation increased ANP expression in LV (75%), in RV (74%) and increased a-skelectal expression in LV (300%) and in RV (546%). Baroreflex function impairment by SAD, despite not changing BP, induced important adjustments in cardiac structure and pulmonary hypertension. These changes may indicate that isolated baroreflex dysfunction can modulate target tissue damage.