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The effect of a resveratrol-rich wine on LDL oxidation
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ANTIPHOSPHOLIPID ANTIBODIES A RISK FACTOR F O R ATHEROSCLEROSIS?
T. Reshetnyak 1, T. Popkova 1, T. Tichonova1, L. Patrushev4, T. Kovalenko 4, E. Match 1, I. Oserova3, N. Perova 3, O Fomicheva2, E. Alexandrova2, V. Nassonova1, E. Nassonov1. 1Institute of Rheumatology RAMS; 2Institute
of Cardiology, 3Center of Prophylactic Medicine, 4Shemyakin Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia Aim: To evaluate serum lipid parameters in patients with primary and secondary antiphospholipid syndrome (APS) and association between its abnormal levels, other risk factor of thrombosis with antiphospholipid antibodies and atherosclerosis. Patients and Methods: Three groups were formed. The first group included 23 patients with PAPS, second group 33 SLE+APS pts, and the third group 35 healthy donors. Atherosclerosis was assed with B-mode ultrasonography examination. Coronarography and scintigraphy with TL-201 were done in 9 pts. with myocardial infarction (MI). Genomic testing was performed for factor VR506Q (factor V Leiden), 3'prothrombin (G20210A) and 5,10 methylenetetrahydrofolate reductase (MTHFR) polymorphism as risk factors for thrombosis. Results: Thrombotic events were registered in 19 of 23 pts from the first group and in 23 of 33 from the second group. Elevated levels of total cholesterol and LDL-CH were found in 23 of 56 studied pts. (11 with PAPS and 12 with SLE+APS). These findings were associated with arterial thrombotic events: 11 of these 23 patients with abnormal lipid parameters had thrombosis in cerebral and coronary artery. Abnormal lipid parameters in SLE+APS pts were associated with activity of SLE and corticosteroids treatment. Presence of factor VR306Q, G20210A, MTHFR polymorphisms were associated with recurrent thrombosis. Conclusion: Activity of SLE, long time use of corticosteroids and antiphospholipid antibodies is significant risk factor for atherosclerosis independent of the classic risk factors of hypertension, tobacco use and abnormal lipid parameters. ~THE
EFFECT OF A RESVERATROL-RICH WINE ON LDL OXIDATION
A.E Revell 1, M. Legge 1, W.H.E Sutherland2, S.RA. McCormick 1.
JDepartment of Biochemistry, 2Department of Medicine, University of Otago, Dunedin, New Zealand Oxidised low density lipoprotein (LDL) is a known feature of the atherosclerotic plaque where it contributes to the development of fatty lesions. It is thought that consumption of dietary antioxidants should prevent LDL oxidation and thus reduce the development of atherosclerosis. Red wine contains a number of phenolic compounds that have antioxidant properties. Indeed, the daily consumption of red wine is thought to be responsible for the low rate of atherosclerosis in the French people. In particular, the phenolic compound resveratrol, has been proposed as one of the most active cardioprotective elements in red wine. Resveratrol is produced in grape skins in a highly variable manner and concentrations in red wine range from 0 to 15 mg/L. We have measured the levels of the phenolic compounds, resveratrol, catechin, epicatechin and quercetin in New Zealand red wines. A wine with high levels of resveratrol (9.75 mg/L), catechin (211 mg/L), epicatechin (227 mg/L) and quercetin (12.33 mg/L), was analysed for its ability to prevent the copper-mediated oxidation of LDL alongside pure solutions of all four phenolic compounds. The red wine and pure phenolic compounds were all effective inhibitors of LDL oxidation in vitro. However, only the red wine was able to protect LDL from oxidation ex vivo. Our results show that resveratrol, catechin, epicatechin and quercetin do not associate with the LDL particle and are therefore unlikely to protect LDL from oxidation in vivo. Our results do, however, indicate the presence of other antioxidant compounds in red wine that do associate with LDL and may protect against oxidation. We are currently investigating this further. ~5]
PHENOTYPE AND GENOTYPE IN HOMOZYGOUS AND COMPOUND HETEROZYGOUS FH PATIENTS
G. Reyes 1, S Castillo 1, R Mozas 1, D. Tejedor 1, E Civeira 2, R. Alonso 2, R Mata 2, E Almagro 2, M. Franco 2, J. Tebar 2, M. Pocovl 1. 1Department
of Biochemistry and Molecular Biology, University of Zaragoza; 2The Spanish Group of FH (www.colesterolfamiliar.com), Spain Familial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the encoding gene for the low density lipoprotein
receptor (LDL-R) with an incidence in general population of 1:500 for heterozygous form and 1:1000.000 for homozygotes. The existence of a broad variability between the phenotypic expression and the elevated cholesterol levels in this disorder is word-wide accepted; at least, an important part of this variability is determined by the type of the LDL-R gene mutation. In order to identify genotype-phenotype relationship, we analysed the LDL-R gene mutations in 378 unrelated Spanish subjects, which had been previously classified using MedPed criteria as FH patients. We characterizated four homozygous ([2393de19+N543H] + [2393de19+ N543H]; [1045delC] + [1045delC]; [R574W] + [R574W]; [Q427X] + [Q427X]; and three compound heterozygous ([E256K] + [Y421X]; [W18X+E256K] + [E256K]; [W-18X+E256K] + [2393de19 + N543H]) patients. Although all of them presented an important elevation of their total and LDL cholesterol levels (LDL-C), patients for nonsense mutations presented the highest plasma LDL-C levels. In addition, nonsense mutations carriers were more prone to premature coronary artery disease and presence of xanthomas than missense mutations or 9bp inframe deletion carriers. In conclusion, the nature of the LDL-R gene in homozygous and compound heterozygous FH reflect in part the clinical phenotype in these patients. ~fS-~ THE APOLIPOPROTEIN A-V GENE PREDISPOSES TO H I G H PLASMA TRIGLYCERIDES IN FAMILIAL COMBINED HYPERLIPIDEMIA J. Ribalta 1, L. Figuera2, J. Fernandez-Ballart 3, E. Vilella 2, M. Castro Cabezas4, L. Masana 1, J. Joven2. IUnitat de Recerca de Lipids
i Arteriosclerosi, 2Centre de Recerca Biom~dica, 3Unitat de Medicina Preventiva i Salut P{tblica, Institut de Recerca en Ciencies de la Salut, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain," 4Department of Vascular Medicine, University Medical Center, Utrecht, The Netherlands Background: Familial combined hyperlipidemia (FCHL) is the commonest form of hereditary hypeflipidemia and it is considered a significant genetic risk factor for developing cardiovascular disease. Its genetic basis is not known but the AI-CIII-AIV gene cluster has been repeatedly associated with FCHL as a site involved in modulating the expression of the hyperlipidemia. We have analyzed the potential link beetwen the newly identified apolipoprotein AV gene (APOAV), adjacent to the AI-CIII-AIV gene cluster, and FCHL. Methods and Results: A single nucleotide polymorphism C/T in the APOAV was used as the genetic marker to search for associations between the APOAV and TG metabolism in 16 FCHL families (n-103), a populationbased control group (n-408) and a normolipidemic control group (n-89). The APOAV variant was 2.7-fold higher among FCHL hyperlipidemics than in their normolipidemic relatives and 2-fold more frequent than in the general population. Among FCHL familiy members those carrying the APOAV rare allele had a 3.25 times higher risk of developing the disease and had an average of 30% higher fasting plasma triglycerides. However, the association of APOAV with increased TG in the general population was very limited and completely absent in individuals selected as normolipemics. Conclusion: We propose the newly identified APOAV as a predisposition factor for hypertriglyceridemia in FCHL. ~fS-~ CIRCULATING CELL ADHESION MOLECULES IN DEPENDENCE ON AGE AND CARDIOVASCULAR RISK V. Richter 1, F. Rassoul 1, K. Purschwitz 1, B. Hentschel 1, W. Reuter2, T. Kuntze 3, B. Kloetzer4. 1 University of Leipzig, Institute of Laboratory
Medicine," 2University Hospital Leipzig, Clinic of Internal Medicine IV; 3University of Leipzig, Heartcenter," 4 University Hospital Leipzig, Clinic of Surgery II, Leipzig, Germany Elevated levels of circulating cell adhesion molecules (cCAMs) are found in subjects with vascular disease and in subjects with several risk factors for atherosclerosis. However, data evaluating cCAMs and biological age are limited. The purpose of this study was to assess in subjects with different cardiovascular risk profiles the levels of cVCAM-1 (circulating vascular cell adhesion molecule-l), cICAM-1 (circulating intercellular adhesion molecule-l), and cE-selectin in dependence on age. The following groups of subjects were included in the study: 287 apparently healthy subjects of the average population aged 18 89 years, 80 vegetarians which are characterized by a favourable global cardiovascular risk profile, 92 patients with coronary heart disease, and 181 patients with peripheral arterial
73rd EAS Congress
•
Reshe~yak
3
]
I
S
ANTIPHOSPHOLIPID ANTIBODIES A RISK FACTOR F O R ATHEROSCLEROSIS?
T. Reshetnyak 1, T. Popkova 1, T. Tichonova1, L. Patrushev4, T. Kovalenko 4, E. Match 1, I. Oserova3, N. Perova 3, O Fomicheva2, E. Alexandrova2, V. Nassonova1, E. Nassonov1. 1Institute of Rheumatology RAMS; 2Institute
of Cardiology, 3Center of Prophylactic Medicine, 4Shemyakin Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia Aim: To evaluate serum lipid parameters in patients with primary and secondary antiphospholipid syndrome (APS) and association between its abnormal levels, other risk factor of thrombosis with antiphospholipid antibodies and atherosclerosis. Patients and Methods: Three groups were formed. The first group included 23 patients with PAPS, second group 33 SLE+APS pts, and the third group 35 healthy donors. Atherosclerosis was assed with B-mode ultrasonography examination. Coronarography and scintigraphy with TL-201 were done in 9 pts. with myocardial infarction (MI). Genomic testing was performed for factor VR506Q (factor V Leiden), 3'prothrombin (G20210A) and 5,10 methylenetetrahydrofolate reductase (MTHFR) polymorphism as risk factors for thrombosis. Results: Thrombotic events were registered in 19 of 23 pts from the first group and in 23 of 33 from the second group. Elevated levels of total cholesterol and LDL-CH were found in 23 of 56 studied pts. (11 with PAPS and 12 with SLE+APS). These findings were associated with arterial thrombotic events: 11 of these 23 patients with abnormal lipid parameters had thrombosis in cerebral and coronary artery. Abnormal lipid parameters in SLE+APS pts were associated with activity of SLE and corticosteroids treatment. Presence of factor VR306Q, G20210A, MTHFR polymorphisms were associated with recurrent thrombosis. Conclusion: Activity of SLE, long time use of corticosteroids and antiphospholipid antibodies is significant risk factor for atherosclerosis independent of the classic risk factors of hypertension, tobacco use and abnormal lipid parameters. ~THE
EFFECT OF A RESVERATROL-RICH WINE ON LDL OXIDATION
A.E Revell 1, M. Legge 1, W.H.E Sutherland2, S.RA. McCormick 1.
JDepartment of Biochemistry, 2Department of Medicine, University of Otago, Dunedin, New Zealand Oxidised low density lipoprotein (LDL) is a known feature of the atherosclerotic plaque where it contributes to the development of fatty lesions. It is thought that consumption of dietary antioxidants should prevent LDL oxidation and thus reduce the development of atherosclerosis. Red wine contains a number of phenolic compounds that have antioxidant properties. Indeed, the daily consumption of red wine is thought to be responsible for the low rate of atherosclerosis in the French people. In particular, the phenolic compound resveratrol, has been proposed as one of the most active cardioprotective elements in red wine. Resveratrol is produced in grape skins in a highly variable manner and concentrations in red wine range from 0 to 15 mg/L. We have measured the levels of the phenolic compounds, resveratrol, catechin, epicatechin and quercetin in New Zealand red wines. A wine with high levels of resveratrol (9.75 mg/L), catechin (211 mg/L), epicatechin (227 mg/L) and quercetin (12.33 mg/L), was analysed for its ability to prevent the copper-mediated oxidation of LDL alongside pure solutions of all four phenolic compounds. The red wine and pure phenolic compounds were all effective inhibitors of LDL oxidation in vitro. However, only the red wine was able to protect LDL from oxidation ex vivo. Our results show that resveratrol, catechin, epicatechin and quercetin do not associate with the LDL particle and are therefore unlikely to protect LDL from oxidation in vivo. Our results do, however, indicate the presence of other antioxidant compounds in red wine that do associate with LDL and may protect against oxidation. We are currently investigating this further. ~5]
PHENOTYPE AND GENOTYPE IN HOMOZYGOUS AND COMPOUND HETEROZYGOUS FH PATIENTS
G. Reyes 1, S Castillo 1, R Mozas 1, D. Tejedor 1, E Civeira 2, R. Alonso 2, R Mata 2, E Almagro 2, M. Franco 2, J. Tebar 2, M. Pocovl 1. 1Department
of Biochemistry and Molecular Biology, University of Zaragoza; 2The Spanish Group of FH (www.colesterolfamiliar.com), Spain Familial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the encoding gene for the low density lipoprotein
receptor (LDL-R) with an incidence in general population of 1:500 for heterozygous form and 1:1000.000 for homozygotes. The existence of a broad variability between the phenotypic expression and the elevated cholesterol levels in this disorder is word-wide accepted; at least, an important part of this variability is determined by the type of the LDL-R gene mutation. In order to identify genotype-phenotype relationship, we analysed the LDL-R gene mutations in 378 unrelated Spanish subjects, which had been previously classified using MedPed criteria as FH patients. We characterizated four homozygous ([2393de19+N543H] + [2393de19+ N543H]; [1045delC] + [1045delC]; [R574W] + [R574W]; [Q427X] + [Q427X]; and three compound heterozygous ([E256K] + [Y421X]; [W18X+E256K] + [E256K]; [W-18X+E256K] + [2393de19 + N543H]) patients. Although all of them presented an important elevation of their total and LDL cholesterol levels (LDL-C), patients for nonsense mutations presented the highest plasma LDL-C levels. In addition, nonsense mutations carriers were more prone to premature coronary artery disease and presence of xanthomas than missense mutations or 9bp inframe deletion carriers. In conclusion, the nature of the LDL-R gene in homozygous and compound heterozygous FH reflect in part the clinical phenotype in these patients. ~fS-~ THE APOLIPOPROTEIN A-V GENE PREDISPOSES TO H I G H PLASMA TRIGLYCERIDES IN FAMILIAL COMBINED HYPERLIPIDEMIA J. Ribalta 1, L. Figuera2, J. Fernandez-Ballart 3, E. Vilella 2, M. Castro Cabezas4, L. Masana 1, J. Joven2. IUnitat de Recerca de Lipids
i Arteriosclerosi, 2Centre de Recerca Biom~dica, 3Unitat de Medicina Preventiva i Salut P{tblica, Institut de Recerca en Ciencies de la Salut, Hospital Universitari de Sant Joan, Universitat Rovira i Virgili, Reus, Spain," 4Department of Vascular Medicine, University Medical Center, Utrecht, The Netherlands Background: Familial combined hyperlipidemia (FCHL) is the commonest form of hereditary hypeflipidemia and it is considered a significant genetic risk factor for developing cardiovascular disease. Its genetic basis is not known but the AI-CIII-AIV gene cluster has been repeatedly associated with FCHL as a site involved in modulating the expression of the hyperlipidemia. We have analyzed the potential link beetwen the newly identified apolipoprotein AV gene (APOAV), adjacent to the AI-CIII-AIV gene cluster, and FCHL. Methods and Results: A single nucleotide polymorphism C/T in the APOAV was used as the genetic marker to search for associations between the APOAV and TG metabolism in 16 FCHL families (n-103), a populationbased control group (n-408) and a normolipidemic control group (n-89). The APOAV variant was 2.7-fold higher among FCHL hyperlipidemics than in their normolipidemic relatives and 2-fold more frequent than in the general population. Among FCHL familiy members those carrying the APOAV rare allele had a 3.25 times higher risk of developing the disease and had an average of 30% higher fasting plasma triglycerides. However, the association of APOAV with increased TG in the general population was very limited and completely absent in individuals selected as normolipemics. Conclusion: We propose the newly identified APOAV as a predisposition factor for hypertriglyceridemia in FCHL. ~fS-~ CIRCULATING CELL ADHESION MOLECULES IN DEPENDENCE ON AGE AND CARDIOVASCULAR RISK V. Richter 1, F. Rassoul 1, K. Purschwitz 1, B. Hentschel 1, W. Reuter2, T. Kuntze 3, B. Kloetzer4. 1 University of Leipzig, Institute of Laboratory
Medicine," 2University Hospital Leipzig, Clinic of Internal Medicine IV; 3University of Leipzig, Heartcenter," 4 University Hospital Leipzig, Clinic of Surgery II, Leipzig, Germany Elevated levels of circulating cell adhesion molecules (cCAMs) are found in subjects with vascular disease and in subjects with several risk factors for atherosclerosis. However, data evaluating cCAMs and biological age are limited. The purpose of this study was to assess in subjects with different cardiovascular risk profiles the levels of cVCAM-1 (circulating vascular cell adhesion molecule-l), cICAM-1 (circulating intercellular adhesion molecule-l), and cE-selectin in dependence on age. The following groups of subjects were included in the study: 287 apparently healthy subjects of the average population aged 18 89 years, 80 vegetarians which are characterized by a favourable global cardiovascular risk profile, 92 patients with coronary heart disease, and 181 patients with peripheral arterial
73rd EAS Congress