PAULO MAGNO MARTINS DOURADO
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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 CarlosIntroduction: 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 levelsconferenceObject 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, AntonioIntroduction: 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- Lack of beta(2)-adrenoceptors aggravates heart failure-induced skeletal muscle myopathy in mice(2014) VOLTARELLI, Vanessa A.; BECHARA, Luiz R. G.; BACURAU, Aline V. N.; MATTOS, Katt C.; DOURADO, Paulo M. M.; BUENO JR., Carlos R.; CASARINI, Dulce E.; NEGRAO, Carlos E.; BRUM, Patricia C.Skeletal myopathy is a hallmark of heart failure (HF) and has been associated with a poor prognosis. HF and other chronic degenerative diseases share a common feature of a stressed system: sympathetic hyperactivity. Although beneficial acutely, chronic sympathetic hyperactivity is one of the main triggers of skeletal myopathy in HF. Considering that (2)-adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle, we presently evaluated the contribution of (2)-adrenoceptors for the morphofunctional alterations in skeletal muscle and also for exercise intolerance induced by HF. Male WT and (2)-adrenoceptor knockout mice on a FVB genetic background (2KO) were submitted to myocardial infarction (MI) or SHAM surgery. Ninety days after MI both WT and 2KO mice presented to cardiac dysfunction and remodelling accompanied by significantly increased norepinephrine and epinephrine plasma levels, exercise intolerance, changes towards more glycolytic fibres and vascular rarefaction in plantaris muscle. However, 2KO MI mice displayed more pronounced exercise intolerance and skeletal myopathy when compared to WT MI mice. Skeletal muscle atrophy of infarcted 2KO mice was paralleled by reduced levels of phosphorylated Akt at Ser 473 while increased levels of proteins related with the ubiquitin--proteasome system, and increased 26S proteasome activity. Taken together, our results suggest that lack of (2)-adrenoceptors worsen and/or anticipate the skeletal myopathy observed in HF.
conferenceObject 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, AntonioBackground: 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.conferenceObject 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.conferenceObject Anti-inflammatory properties of HDL after short-term exercise training without any specific diet in patients with metabolic syndrome(2012) CHAGAS, Antonio C.; TROMBETTA, Ivani C.; DOURADO, Paulo M.; CASELLA, Lia B.; DENARDI, Celise A.; NEGRAO, Carlos E.; CASELLA FILHO, Antonio