ANTONIO CASELLA FILHO

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Autor e Coautores FMUSP-HC Normalizados: CARLOS ALEXANDRE WAINROBER SEGRE ×

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  • conferenceObject
    Influence of the concentration and molecular composition on the LDL and HDL functional characteristics in patients with the metabolic syndrome
    (2012) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; CASELLA, Lia B.; DENARDI, Celise; DOURADO, Paulo; SEGRE, Alexandre; ROEVER-BORGES, Leonardo; NEGRAO, Carlos Eduardo; MARANHAO, Raul; CHAGAS, Antonio Carlos
    Introduction: Long-term exercise associated with diet changes lipoproteins plasma levels. Objectives: We sought to analize the effects of short-term exercise training without any specific diet (T) on the concentration,composition and functional characteristics of LDL and HDL in patients with metabolic syndrome (MS). Methods: Forty sedentary persons were studied,30 with MS and 10 controls.Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer.LDL and HDL subfractions were obtained by plasma ultracentrifugation 1 and their compositions were analyzed. LDL from control subjects was incubated with HDL2a,HDL3b from the MS patients (before and after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C-phospholipid, 3 H-triglycerides, 14 C-cholesterol and 3 H-cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE the HDL-containing supernatant was counted for radioactivity to verify the HDL ability to accept lipids. 2 Results: T decreased triglycerides (TG) but did not change apoB,apoA-I,LDL-C and HDL-C plasma levels. LDL resistance to oxidation increased (+91%) after T,associated with a decrease in the LDL content of apoB (-16%) and TG (-14%) and in the concentration of the small and dense LDL particles. Oxidizability of control LDL decreased when mixed with HDL2a or 3b from patients with MS, before vs. after T (-23% for HDL2a and -18% for HDL3b),associated with an increase in PON1 activity in the MS group (58.3±36.2 before vs.70.7±38.4ng/ml/min after T, p<0.05) and with a significant decrease in the content of total cholesterol (TC) and TG in HDL3b and HDL3c but with an increase in cholesterol ester (CE) in HDL3b. T did not significantly modify concentrations of TC and TG in HDL2a, 2b and 3a. Phospholipids and total protein content did not change in all HDL subfractions.T significantly increased free cholesterol and CE transfer from LDE to HDL in MS group to levels similar to those observed in controls. Conclusion: In patients with the MS, T influences the LDL and HDL functionality by earlier changes in molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating the functional aspects of the lipoproteins besides their plasma levels
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    LIPID TRANSFER TO HDL IN PATIENTS WITH CORONARY ARTERY DISEASE
    (2014) SPRANDEL, Mar lia O.; HUEB, Whady; CASELLA-FILHO, Antonio; SCUDELER, Thiago; REZENDE, Paulo; LIMA, Eduardo; SEGRE, Alexandre; CARVALHO, Ana; MARANHAO, Raul; KALIL-FILHO, Roberto
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    RELATIONSHIPS BETWEEN HDL FUNCTIONAL CHARACTERISTICS AND ENDOTHELIAL VASCULAR FUNCTION AFTER SHORT-TERM EXERCISE TRAINING IN PATIENTS WITH THE METABOLIC SYNDROME
    (2013) CASELLA-FILHO, Antonio; TROMBETTA, Ivani C.; DOURADO, Paulo; LEITE-JUNIOR, Antonio C.; JONKE, Vivian; SEGRE, Alexandre; SANTOS, Raul; NEGRAO, Carlos E.; MARANHAO, Raul C.; CHAGAS, Antonio
    Introduction: Endothelial dysfunction, leading to vasodilation impairment and atherosclerosis, frequently affects patients with metabolic syndrome (MS). A recent study showed that HDL estimulates endothelial nitric oxide synthase (eNOS: a key regulator of vascular nitric oxide production) by activation of Akt and MAP kinases in cultured endothelial cells. Objectives: To investigate the relationships between HDL characteristics (concentration, composition, functionality) on the eNOS availability and endothelial vascular function in patients with MS after a short-term exercise training (T). Methods: Forty sedentary persons (30 MS and 10 controls) were studied. Twenty with MS were subjected to a 3 times/week of a training load (45min/d) for 3 months on a bicycle. Cyclic guanosine monophosphate (cGMP), blood nitrite concentrations (biomarkers of eNOS availability) and HDL subfractions obtained by plasma ultracentrifugation were analyzed. A control LDL was incubated with HDL subfractions from the patients with MS (before-after T) and the in vitro resistance to oxidation was verified. An artificial radio-labeled lipoprotein emulsion was incubated with plasma from the participants. After precipitation of VLDL and LDL, the HDL containing supernatant was counted for radioactivity, to verify the HDL ability to accept lipids. Endothelial vascular function was assessed from forearm blood flow-mediated responses to vasodilation tests (FMD). Results: T did not change HDL-C concentration but changed the molecular composition and improved the functional characteristics of the HDL-particles subfractions: protecting LDL against oxidation (+21%) and increasing the HDL-particles ability to accept lipids (+23%). T increased cGMP and blood nitrite concentrations. The best HDL functional results were associated with the highest cGMP and blood nitrite concentrations and with the best FMD improvement results in the MS group. Conclusions: T early changes functional characteristics of HDL-particles, rather than HDL-C concentration, associated with eNOS biomarkers and with endothelial vascular function improvement in patients with MS, highlighting the early vascular benefits of exercising
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    SHORT-TERM EXERCISE TRAINING CHANGES TRIGLYCERIDES MOLECULAR CONTENT OF THE LDL AND HDL PARTICLES AFFECTING THEIR FUNCTIONAL CHARACTERISTICS IN METABOLIC SYNDROME
    (2013) CASELLA-FILHO, Antonio; TROMBETTA, Ivani; DOURADO, Paulo Magno; LEITE-JUNIOR, Antonio Carlos; SPRANDEL, Marilia C. O.; SEGRE, Alexandre; SANTOS, Raul; NEGRAO, Carlos Eduardo; MARANHAO, Raul C.; CHAGAS, Antonio
    Background: Long–term exercise training associated with diet changes lipoproteins plasma levels. Objectives: We sought to investigate the effects of short–term exercise training without any specific diet (T) on the concentration, composition and functional characteristics of LDL and HDL particles in patients with metabolic syndrome (MS). Methods: Forty sedentary persons (30 MS and 10 controls) were studied. Twenty of those with MS were subjected to a 3 times/week controlled training load (45 min/day) for 3 months on a bicycle ergometer. LDL and HDL subfractions were obtained by plasma ultracentrifugation and their compositions were analyzed. The in vitro resistance to oxidation of the LDL from the patients with MS (before and after T) was verified. A control LDL was incubated with HDL2a and HDL3b from the patients with MS (before – after T) and the in vitro resistance to oxidation was verified. An artificial lipoprotein emulsion (LDE) labeled with 14C–phospholipid, 3H–triglycerides, 14C–cholesterol and 3H–cholesteryl ester was incubated with plasma from the participants. After precipitation of VLDL, LDL and LDE, the HDL–containing supernatant was counted for radioactivity, to verify the HDL ability to accept lipids. Results: T decreased triglycerides (TG) but did not change LDL–C and HDL–C plasma levels. The LDL resistance to oxidation of the MS group increased (+91%) after T, associated with a significant decrease in the LDL–particles content of TG (−14%) and apoB (−16%), and with a 27% reduction of the small and dense LDL–particles plasma levels. The oxidizability of the control LDL decreased when mixed with HDL2a or HDL3b from patients with MS, before vs. after T (−23% for HDL2a and −18% for HDL3b) associated with a significant decrease in the content of TG in HDL3b (−12%) and HDL3c (−15%). The transference of TG to HDL normalized after T in the MS group. Conclusions: In patients with MS, T early reduces TG concentration influencing the LDL and HDL functionality by changing their molecular composition rather than their concentration, emphasizing the early benefits of exercise and highlighting the importance of evaluating lipoproteins composition and functional aspects besides their plasma levels.
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    Lipid Transfer to HDL in Patients With Coronary Artery Disease
    (2013) SPRANDEL, Marilia C.; HUEB, Whady; CASELLA-FILHO, Antonio; SEGRE, Carlos A.; CARVALHO, Ana Luiza O.; REZENDE, Paulo C.; CESAR, Luiz A.; RAMIRES, Jose A.; KALIL FILHO, Roberto; MARANHAO, Raul C.
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    LIPID TRANSFER TO HIGH DENSITY LIPOPROTEINS IN TYPE 2 DIABETIC PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE
    (2012) SPRANDEL, Marilia C. O.; HUEB, Whady; CASELLA-FILHO, Antonio; SEGRE, Alexandre; REZENDE, Paulo Cury; CARVALHO, Ana L. O.; FAVARATO, Desiderio; MARANHAO, Raul C.; RAMIRES, Jose; KALIL-FILHO, Roberto
    Background In type 2 diabetes mellitus (DM2), HDL-cholesterol is diminished and it is important to understand the functional and metabolic changes existing in HDL in DM2 patients that may predispose to coronary artery disease (CAD). Lipid transfers between HDL and the other lipoproteins, mediated by cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), are crucial steps in HDL formation and role in reverse cholesterol transfer. Objective Investigate whether development of CAD in DM2 patients are associated with alterations in lipid transfers to HDL and in content of free cholesterol in the plasma. Methods 78 patients with DM2 and CAD (DM2-CAD) and 78 with DM2 without CAD, as diagnosed by cineangiography, were studied. They were of both genders, aged 40-80 yrs. Plasma was incubated for 1h at 37oC with a donor nanoemulsion labeled with 3H -cholesteryl-esters and14C -phospholipids or with 14C-free-cholesterol and 3H -triglycerides. Radioactive lipids transferred from the donor nanoemulsion to HDL were measured in the supernatant after chemical precipitation of non-HDL fractions and the nanoemulsion. Results are % of the total radioactivity of each lipid in HDL. Results In DM2-CAD, LDL-cholesterol and triglycerides were higher than in DM2; HDL-cholesterol was lower. Compared to DM2, DM2-CAD showed diminished transfer to HDL of free-cholesterol (DM2-CAD=4.23±0.24; DM2= 5.66±0.14, p<0.0001) and of triglycerides (1.65±0.13 vs 3.08±0.11, p<0.0001), whereas cholesteryl-ester transfer was increased (3.67±0.16 vs 2.25±0.13, p<0.0001); phospholipid transfer was equal (15.37±0.60 vs15.18±0.20, p=0.76). CETP concentration was equal, while plasma free-cholesterol was higher in DM2-CAD (DM2-CAD=36.9±0.9; DM2=33.1±0.7, p=0.003).HDL particle diameter was equal in both groups. Conclusion The reduction of free-cholesterol transfer to HDL may hinder cholesterol esterification and reverse cholesterol transport. Alterations in triglyceride and cholesteryl-ester transfer may affect lipoprotein stability. Those disturbances in HDL metabolism may facilitate CAD development in DM2. ACC Oral Contributions McCormick Place South, S100c Sunday, March 25, 2012, 9:04 a.m.-9:17 a.m. Session Title: Prevention: Focus on Lipids Abstract Category: 9. Prevention: Clinical Presentation Number: 911-8
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    Lipid Transfer to Hdl in Type 2 Diabetic Patients With and Without Coronary Artery Disease
    (2013) SPRANDEL, Marilia C.; HUEB, Whady; CASELLA-FILHO, Antonio; SEGRE, Carlos A.; CARVALHO, Ana Luiza O.; REZENDE, Paulo C.; CESAR, Luiz A.; RAMIRES, Jose A.; KALIL FILHO, Roberto; MARANHAO, Raul C.
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    THE TRIGLYCERIDE/HDL RATIO REMAINS AS AN INDEPENDENT PLASMA LIPID MARKER OF MAJOR CARDIOVASCULAR EVENTS IN DIABETIC PATIENTS 10-YEAR FOLLOW-UP FROM THE MEDICINE ANGIOPLASTY OR SURGERY STUDY II (MASS II) TRIAL
    (2012) CASELLA-FILHO, Antonio; HUEB, Whady; JONKE, Vivian; SANTOS, Raul; FAVARATO, Desiderio; LIMA, Eduardo; SEGRE, Alexandre; REZENDE, Paulo Cury; GARZILLO, Cibele Larrosa; CHACRA, Ana P. M.; RAMIRES, Jose; KALIL-FILHO, Roberto
    Background: The second Medical, Angioplasty, or Surgery Study (MASS II) compared the long-term effects of medical treatment (MT), angioplasty (PCI), or surgical strategies (CABG) among patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function who were appropriate candidates for all 3 therapies. Plasma lipids are important risk factors for cardiovascular events in CAD patients, especially in diabetics. We showed previously that the TG/HDL ratio was the only parameter independently associated with major cardiovascular events (MACE; overall death, myocardial infarction, and unstable angina that required myocardial revascularization) in patients after the 10-year follow up of stable CAD patients in the MASS II. In this analysis we evaluated the association of plasma lipids with MACE in diabetic patients after a 10-year follow-up of the MASS II. Methods: The data of 200 patients of the MASS II, 100 diabetics and 100 non diabetics, were analyzed for risk factors and plasma lipids levels. The levels of fasting plasma lipids were determined at baseline and 6 months after randomization. It was instituted in all study patient groups the same lipid therapy. Concentrations of total cholesterol, HDL, non-HDL and LDL-cholesterol as well as LDL/HDL, and TG/HDL ratios were divided according to distribution quartiles. The association of plasma lipids at baseline and at 6 months with MACE was determined by Cox regression models. Results: The patients were followed up for an average of 11.4 years. In the subgroup of diabetic patients, after adjustment for confounders, older age (> 65 years old), randomized treatment for CAD (CABG vs. MT) and the TG/HDL ratio determined at 6 months were independently associated with MACE. There was no association between MACE and other plasma lipids. Conclusions: The TG/HDL remains as a lipid parameter independently associated with MACE in diabetic patients after the 10-year follow up of stable CAD patients in the MASS II.
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    Anti-inflammatory properties of HDL after short-term exercise training in patients with metabolic syndrome
    (2012) CASELLA-FILHO, A.; TROMBETTA, I. C.; CASELLA, L. B.; DOURADO, P. M. M.; SEGRE, A.; FAVARATO, D.; ROEVER-BORGES, L.; NEGRAO, C. E.; MARANHAO, R. C.; CHAGAS, A. C. P.
    Background: Recent study showed that short-term exercise, associated with diet and weight loss, improves the anti-inflammatory properties of HDL in metabolic syndrome (MS). However, diet and weight loss, per se, can alter the functionality of HDL and, in real life, many patients do not follow the medical counseling of diet and exercise simultaneously. We showed previously that the antioxidative characteristics and the capacity to accept lipids of HDL are early improved by short-term exercise training (Tr) with no diet associated. We sought to verify whether the anti-inflammatory properties of HDL are affected by Tr, without any diet associated, in patients with MS. Methods: Forty sedentary persons (30 with MetS,10 controls) were evaluated. Twenty of those with MS were subjected to a 3 times/week training load (45 min/day) for 3 months on a bicycle. Plasma high-sensitivity C-reactive protein (hs-CRP) was analyzed and HDL sub-fractions were obtained by plasma ultracentrifugation. Endothelial cells were cultured, stimulated with TNF-α and lipopolysacharide, and coincubated with HDL subfractions obtained before and after Tr. Sequentially, those cultures of endothelial cells were coincubated with THP-1 cells labeled with a fluorescent marker. The labeled THP-1 cells that adhered on endothelial cells were counted under fluoroscopic microscope. Results: Baseline plasma levels of HDL-C were lower in the MS group compared to controls and Tr did not change neither HDL-C nor weight in MS group. Hs-CRP plasma levels from patients with MetS were higher than controls (3.0±1.5 vs 1.5±1.5 mg/L respectively, p<0.05) and did not change after Tr(3.0±1.5 vs 2.8±1.8 mg/L, before and after Tr respectively, p>0.05). The number of adhered labeled THP-1 cells coincubated with endothelial cells did not change significantly when mixed with HDL2a or HDL3b from patients with MS after Tr, compared with HDL2a or HDL3b obtained before Tr. Conclusion: Our results showed that Tr did not change an inflammatory serum marker (hs-CRP) and the adherence of THP-1 cells on endothelium cells, suggesting that the anti-inflammatory properties of HDL are not early improved by short-term exercise, when there is no diet associated.
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    HIGH SENSITIVITY CARDIAC TROPONIN I AS A DIAGNOSTIC TOOL FOR THE PRESENCE OF CORONARY ARTERY DISEASE IN STABLE DIABETIC PATIENTS
    (2014) SEGRE, Alexandre; HUEB, Whady; SPRANDEL, Marilia O.; CASELLA-FILHO, Antonio; FAVARATO, Desiderio; STRUNZ, Celia; VENTURA, Laura; CARVALHO, Ana; MARANHAO, Raul C.; RAMIRES, Jose; KALIL-FILHO, Roberto