5 th Annual Meeting of the Diabetes & Cardiovascular Disease EASD Study group / Diabetes & Metabolism 38 (2012) S89-S116 S101 while the expression CDKN1a at mRNA level is increased (NG vs HG P=0.01). In both cases, GLP-1 does not exert its effects after chronic exposure to high glucose concentration (NG vs NG+GLP-1 P=0.02 and P=0.06, BCL-2 and CDKN1A, respectively. And HG vs HG+GLP-1 P=0.30 and P=0.74, BCL-2 and CDKN1A, respectively). Conclusion: Our preliminary fndings suggest that endothelial cells, after a long of exposure to high glucose, lose their ability to respond normally to the GLP-1 action, in terms of increasing their antioxidant capacity and regulating ER function and UPR response. This effect is probably due to the development of resistance to GLP-1 during high glucose chronic exposure. Grant : FIS PI10/01256 from Instituto Carlos III OP8: Early atherosclerosis in Familial Partial Lipodystrophy of the Dunnigan-type: Endothelial cell dysfunction induced by p.R482W lamin-A G. Bidault 1,2 , M. Garcia 1,2 , M.C. Vantyghem 3 , P.H. Ducluzeau 4 , R. Morichon 5 , K. Thiyagarajah 1,2 , S. Moritz 2 , J. Capeau 1,2,6 , C. Vigouroux 1,2,6 , V. Béréziat 1,2 1 UPMC Univ Paris 06, UMR_S938, F-75005, Paris, France; 2 INSERM UMR_S938, Centre de Recherche Saint-Antoine, Faculté de Médecine Pierre et Marie Curie, Site Saint-Antoine, F-75012, Paris, France; 3 Service d’Endocrinologie et Maladies Métaboliques, INSERM U 859, Centre Hospitalier Régional et 3 Universitaire (CHRU) de Lille, Lille, France; 4  Centre de Recherche en Nutrition Humaine, Hospices Civils, Lyon, France; 5 Institut Fédératif de Recherche en Santé Saint-Antoine IFR-65, Paris, France; 6 AP-HP, Hôpital Tenon, Service de Biochimie et Hormonologie, F-75020, Paris, France Background: Some mutations in LMNA, encoding A-type lamins, are responsible for lipodystrophic syndromes, which present features of severe metabolic syndrome. p.R482 substitutions lead to the Dunnigan familial partial lipodystrophy (FPLD2) while the p.L92F mutation gives a phenotype of metabolic laminopathy (ML). FPLD2 has been associated with precocious atherosclerosis. Methods and Results: We analyzed the cardiovascular phenotype of nineteen patients with FPLD2 and a patient with ML (LMNA p.L92F). Despite similar metabolic alterations, FPLD2 patients, but not the ML patient, presented early atherosclerosis. We then studied the effects of wild-type or mutated p.R482W and p.L92F-prelamin-A overexpression on primary cultured human coronary endothelial cells (HCAECs). Although both mutations led to defects in prelamin-A matu- ration, only p.R482W-prelamin-A was predominantly distributed to the nuclear envelope, in favor of its persistent farnesylation. p.R482W but not wild-type or p.L92F-prelamin-A overexpression led to endothelial dysfunction, with decreased expression of endothelial nitric oxide synthase, increased infammation, and increased endothelial adhesion of peripheral blood mononuclear cells. p.R482W-prelamin-A also induced oxidative stress, increased DNA double-strand breaks and cellular senescence. In vitro pravas- tatin treatment, which inhibits prelamin-A farnesylation, decreased p.R482W-prelamin-A association to the nuclear envelope, oxidative stress and infammation. In addition, anti-oxidants decreased infammation and DNA double-strand breaks occurrence, suggesting that farnesylated p.R482W-prelamin-A induced oxidative stress which resulted in endothelial dysfunction. Conclusions: FPLD2-associated p.R482W but not ML-associated p.L92F lamin-A mutation resulted in farnesylated- prelamin-A accumulation that induced endothelial dysfunction in vitro. These observations suggest that LMNA p.R482 mutations have a direct pro-atherogenic role, contributing to the early occurrence of atherosclerosis in FPLD2. Grant: Funding sources were from INSERM, the Programme National de Recherche sur le Diabète (PNRD/ARD), the EU FP6 Eurolaminopathies project, and the Société Francophone du Diabète. GB is a recipient of a fellowship from the Ministère Français de l’Enseignement Supérieur et de la Recherche. OP9: Diet modulates endogenous thrombin generation, a biological estimate of thrombosis risk, independently of the metabolic status C. Sanchez 1,2,3 , M. Poggi 1,2,3 , P.E. Morange 1,2,3 , C. Defoort 1,2,3 , J.C. Martin 1,2,3 , S. Tanguy 4 , A. Dutour 1,2,3 , M. Grino 1,2,3 , M.C. Alessi 1,2,3 1  Inserm, UMR1062, « Nutrition, Obesity and Risk of Thrombosis », F-13385, Marseille, France; 2  INRA, UMR1260, F-13385, Marseille, France; 3  Aix- Marseille Univ, Faculté de Médecine, F-13385, Marseille, France ; 4 CNRS, TIMC-IMAG UMR 5525, équipe PRETA, F-38706, La Tronche, France Background and aims: The association between obesity and thrombosis might be explained by a hypercoagulable state. In addition, it is still discussed controversially whether obesity, fat diet or metabolic disturbances are the main infuence factors of the changes in the coagulation system. Methods and Results: In this study, we investigated the effect of postnatal overfeeding and high fat diet (HFD) on thrombin generation. Endogenous Thrombin potential (ETP) was measured using the Calibrated Automated Thrombogram. Weaning rats exhibited high ETP values that decreased under low-fat diet (LFD) and remained elevated upon HFD. In adult rats, HFD-induced ETP increase was independent of coagulation factors, obesity and insulin resistance and negatively associated with polyunsaturated fatty acid (PUFA) levels. Switching from HFD to LFD reversed the procoagulant phenotype with a slower kinetic than the normalization of hyperinsulinemia. In humans, ETP was independent of body weight while it was negatively associated with nutritional markers such as the percentage of energy provided by proteins, the protein/fat ratio, and circulating phenolic compounds and omega-3 PUFA. A recommended 3-month healthy diet with reduced energy density, including lipids, decreased ETP (- 21%; P<0.0001). ETP changes were not associated with body weight, insulin sensitivity or coagulation factor variations, but correlated negatively with plasma docosahexaenoic acid, a nutritional status sensitive fatty acid, and compounds refecting vegetable intake. Conclusion: Diet plays a pivotal role in regulating ETP, independently of obesity and insulin resistance. Global nutritional recommendations could be useful in primary prevention of thrombosis. OP10: Analysis of the relationship between the presence of metabolic syndrome with the level of oxidized LDL and impaired fbrinolysis in patients with patients with type 2 diabetes S. Singh, K. Lalic, N. Rajkovic, L.J. Popovic, D. Draskovic, L.J. Stošic, M. Zamaklar Clinic for Endocrinology, Diabetes and Metabolic disease, Clinical centre of Serbia, Belgrade Background and aims: It is known that in patients with type 2 diabetes (T2D) and the metabolic syndrome (MS) there is a higher risk for atherosclerosis. The aim of this study was to investigate the relationship of non-traditional risk factors for atherosclerosis, biomarkers of lipid peroxidation measured by oxidized LDL levels (oxLDL) and markers of fnbrinolisis measured by plasminogen activator inhibitor 1 (PAI-1) in patients with T2D and the MS. © 2021 Elsevier Masson SAS. Tous droits réservés. - Document téléchargé le 27/11/2021 Il est interdit et illégal de diffuser ce document.