183 REGULAR EXERCISE INCREASED PLASMA PRE-BETA 1-HDL CONCENTRATION IN ADULT WOMEN WITH METABOLIC SYNDROME

79th EAS Congress

Atherosclerosis Supplements 12, no. 1 (2011) 13–184

183 REGULAR EXERCISE INCREASED PLASMA PRE-BETA 1-HDL CONCENTRATION IN ADULT WOMEN WITH METABOLIC SYNDROME ˜ 2 , I. Rosety2 , A. Diaz-Ordonez ˜ 3, M. Rosety-Rodriguez1 , F.J. Ordonez M.A. Rosety3 , A. Camacho3 , N. Garcia2 , J. Rosety4 , G. Fornieles-Gonzalez1 . 1 Internal Medicina, 2 Medicina, 3 School of Sport Medicine, University of Cadiz, 4 Urology, Hospital Universitario Puerta del Mar, Cadiz, Spain Background and Aim: Recent studies have shown that the prebeta-1 subclass of high-density lipoprotein particles (pre-beta 1-HDL) may play an important role in the reverse cholesterol transport pathway as the initial acceptors of cellular cholesterol. This study was designed to assess the influence of a 12week aerobic training program in plasma pre-beta 1-HDL concentration in adult women with metabolic syndrome. Methods: Sixty young women (39.1±3.5years; 28.7±1.9kg/m2 ) with metabolic syndrome according to the criteria reported by the National Cholesterol Education Program Adult Treatment Panel III volunteered for this study. Fortyfive were randomly included in experimental group to perform a 12-week aerobic training program, 3 days/week, consisting of warm up (10-min), main part in a treadmill (20−35-min [increasing 5 min each 3 weeks]) at a moderate work intensity of 60−75% of peak heart rate (increasing 5% each 3 weeks) and cooldown (10-min). Control group included 15 age, sex and BMI-matched women with metabolic syndrome that did not perform any training program. Plasma pre-beta 1-HDL levels were measured using ELISA (Daiichi-Pure-Chemicals, Tokyo, Japan) Results: When compared to baseline, plasma pre-beta 1-HDL was increased significantly after a 12-week aerobic training protocol (131.3±11.7 vs. 166.4±13.0 mg/ml serum;p = 0.02). In contrast, no changes were reported in controls. Conclusion: Aerobic training at moderate intensity increased plasma prebeta 1-HDL concentration in women with metabolic syndrome. Further longterm well-conducted studies are required in order to highlight potential clinical benefits of this improvement in these patients. 184 HDL2 LEVELS REDUCE THE ASSOCIATION OF LDL WITH ARTERIAL PROTEOGLYCANS: A NOVEL ANTI-ATHEROSCLEROTIC ROLE OF HDL SUBCLASSES G. Camejo, B. Rosengren, M. Umaerus, E. Hurt-Camejo. Cardiovascular R&D, ¨ AstraZeneca Pharmaceuticals, Molndal, Sweden Aims: Participation in reverse cholesterol transport and anti-oxidative and antiinflammatory properties appear responsible for the atheroprotective properties of ing HDL. In addition, HDL and apoAI have been shown to reduce in vitro the association of LDL with arterial proteoglycans (Camejo et al Acta Med Scand 642:159;1980). Intimal entrapment of LDL by iproteoglycans is a key step in atherogenesis (Tabas et al Circulation 116:1832; 2007), therefore is important to elucidate mechanism by which HDL can interfere with this entrapment. Methods: 1. Serum and plasma from subjects with insulin resistance (IR), obesity or not, and type 2 diabetes (T2D) and controls were used to evaluate the affinity of LDL for isolated arterial proteoglycans and their HDL2 and HDL3 content using ultracentrifugation in D2 O/sucrose isotonic buffers (Stahlman et al J Lipid Res 49: 481, 2008). 2. Isolated HDL2 or HDL3 was added to HDL-free plasma and the amount of LDL complex to proteoglycan was evaluated by measurements of the insolubilized LDL after centrifugation and electrophoresis. Results: 1. In plasma of subjects with the dyslipidemia of IR there is a sinificant linear correlation (r2 = 0.64, p < 0.02) between the absolute content of HDL2 and the amout of LDL/proteoglycan complex formed. 2. Addition of autologous HDL2 at physiological levels, but not HDL3, to LDL-containing plasma inhibit the formation LDL/proteoglycan insoluble complex. Conclusions: HDL2 appears responsible for reducing the association of LDL with arterial proteoglycans. If present in vivo this phenomenon may contribute to the atherogenicity of conditions with low circulating lavels of the HDL2 subclass as in insulin resistance. 185 HDL MODULATES INSULIN SENSITIVITY AND SECRETION DURING ACUTE PHASE OF MYOCARDIAL INFARCTION L.S. Fernandes De Carvalho1 , R.M.R. Cintra1 , A.L.R. Araujo ´ 1 , F.A. Moura1 , J.C.Q.E. Silva1 , O.R. Coelho2 , A.C. Sposito2 . 1 Universidade de Bras´ılia, Brasilia, 2 Cardiology Division, Faculty of Medical Sciences, Unicamp, Campinas, Brazil During myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia which is followed by a substantial increase in mortality. Recent data indicate that HDL modulates insulin sensitivity and secretion. To date, however, the HDL role on stress hyperglycemia remains unknown. We explored the influence of HDL on stress hyperglycemia during acute phase of MI. Consecutive non-diabetic patients with ST-elevation MI

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(n = 183) were selected from the Brasilia Heart Study for this investigation. Plasma insulin, glucose and C-peptide were measured in the first 24 hours and at the fifth day after MI onset. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31−38, Q3: 38−47 and Q4: >47 mg/dL). On admission, no difference was found between the quartiles in plasma glucose (p = 0.6), insulin (p = 0.6), C-peptide (p = 0.5), HOMA2S (p = 0.9) and HOMA2B (p = 1.0). On the fifth day there was a reduction in blood glucose whose intensity was directly proportional to HDL-C quartile (−1±32, −13±46, −19±25, −27±21; respectively, p < 0.001). In parallel, there was a reduction in plasma insulin [−7.1 (−25, +1), −5.5 (−22, −1), −9.9 (−26, −1), −17.7 (−32, −9); respectively, p < 0.001] and C-peptide [0 (−3, +1), −1.2 (−3, +1), −1.7 (−3.0), −2.4 (−4.0); respectively, p < 0.001] whose magnitude was inversely proportional to HDL-C quartile. Consistently, the change in HOMA2S [+1 (−11, +15), +7 (−15, +17), +10 (−5, +30), +15 (−8, +28); respectively, p < 0.001] and HOMA2B [−11 (−43, +31), +16 (−45, +48), +22 (−8, +44), +24 (−23, +61); respectively, p = 0.01] were also proportional to HDL-C quartiles. This study provides the first evidence that elevated HDL plasma levels may attenuate stress hyperglycemia during MI via acceleration of the improvement in insulin secretion and sensitivity. 186 NOVEL ABCA1 MUTATIONS IN L PATIENTS WITH SEVERE HDL DEFICIENCY WITH OR WITHOUT CLASSIC MANIFESTATIONS OF TANGIER DISEASE P. Zanoni1 , T. Fasano1 , P.B. Deegan2 , A. Park3 , M.D. Feher4 , F. Gurakan5 , E. Favari6 , F. Bernini6 , S. Calandra1 . 1 Dpt of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy, 2 Dpt of Medicine, 3 Dpt of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge, 4 Dpt of Beta Cell Diabetes Centre, Chelsea and Westminster Hospital, London, UK, 5 Unit of Pediatric Gastroenterology, Hepatology and Nutrition, Hacettepe University Medical Faculty, Ankara, Turkey, 6 Dpt of Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Parma, Italy Biallelic ABCA1 mutations are the cause of Tangier Disease (TD), a rare disorder characterized by extremely low HDL-C levels and accumulation of cholesteryl esters in tissues. We investigated 6 patients with low HDL-C suspected to have TD. Two identical twins presented undetectable HDL-C and facial dysmorphic features. The first twin had died at 36 from CHD, while the second was a 41 yrs male with thrombocytopenia, and splenomegaly. Both were compound heterozygotes for novel ABCA1 mutations (c.1758 ins G, M586>Fs629X and H1600R) that abolished ABCA1 mediated cholesterol efflux in fibroblasts. Two sisters (6 and 37 yrs old) presented with undetectable HDL-C but only the younger had splenomegaly and anemia. They were homozygous for a novel splicing mutation (IVS31−34a>g) that caused the formation of a transcript retaining part of intron 31 and encoding a truncated protein. A 74 yrs old female had very low HDL-C, mild thrombocytopenia, splenomegaly, Type 2 diabetes and angina. She was a simple heterozygous for a known mutation (D1099Y); however, the ABCA1 mediated cholesterol efflux in her fibroblasts was abolished. A 37 yrs old male presented with very low HDL-C, high triglycerides but no clinical manifestations of TD. He was heterozygous for a novel splicing mutation (IVS10−27 g>a), resulting in a mRNA containing part of intron 10 and encoding a truncated protein. We report four novel ABCA1 mutations. The classic signs of TD were not constant among patients with severe HDL deficiency. Intronic mutations, that are not uncommon in patients carrying ABCA1 mutations, represent a diagnostic challenge. 187 SPHINGOSINE KINASE INHIBITION INDUCES BOTH PRO- AND ANTI-ATHEROGENIC EFFECTS IN LOW-DENSITY LIPOPROTEIN RECEPTOR-DEFICIENT MICE S. Costa1 , F. Poti1 , M. Bot2 , V. Bergonzini1 , M. Galletti1 , L. Maynes3 , G. Varga4 , M. Simoni1 , J.-R. Nofer1,5 . 1 Dept. of Medicine, Endocrinology, Metabolism and Geriatrics, University of Modena and Reggio Emilia, Modena, Italy, 2 Division of Biopharmaceutics, Gorlaeus Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands, 3 Apogee Biotechnology Corporation Hershey, Hershey, PW, 5 ¨ Center for Laboratory USA, 4 Institute of Immunology, University of Munster, Medicine, University Hospital Munster, ¨ Munster, ¨ Germany Background: Sphingosine 1-phosphate (S1P), a lysosphingolipid associated with high-density lipoprotein (HDL), contributes to the anti-atherogenic potential attributed to this lipoprotein. This study examined whether a reduction of S1P plasma levels affects atherosclerosis in a murine model of disease. Methods and Results: LDL-R−/− mice on Western diet were given ABC294640, an inhibitor of sphingosine kinases 1 and 2 for 16 weeks at a dose of 50 mg/kg/d. ABC294640 decreased plasma S1P by approx. 30−40%. However, ABC294640 failed to affect atherosclerotic lesion formation. Plasma triglycerides were reduced whereas total and HDL-cholesterol remained unchanged in course of ABC294640 treatment. ABC294640 increased plasma IL-12p70 and IL-12p70