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YI-839 TRANS FATTY ACIDS STIMULATE ATHEROSCLEROSIS ONLY IN THE ABSENCE OF DIETARY CHOLESTEROL
YI Young investigators YI-839
TRANS FATTY ACIDS STIMULATE ATHEROSCLEROSIS ONLY IN THE ABSENCE OF DIETARY CHOLESTEROL
C.M.C. Dupasquier 1,2,3,4,5 , R.S. McCullough 3,5 , D.P. Blackwood 3,5 , J. Adair 3,5 , J.A. Austria 2,3,5 , G.N. Pierce 1,2,3,4,5 . 1 Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada; 2 Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada; 3 St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada; 4 Department of Physiology, Winnipeg, Manitoba, Canada; 5 University of Manitoba, Winnipeg, Manitoba, Canada Epidemiological evidence has associated trans fatty acids (TFAs) in the diet to coronary heart disease. It is assumed that TFAs stimulate atherosclerosis but the only studies to date have shown no effect of TFAs on atherosclerosis. The purpose of this study was to determine the effects of consuming two levels of TFAs, from a commercially hydrogenated vegetable shortening, on atherosclerotic development in the presence or absence of elevated dietary cholesterol. Low-density-lipoprotein receptor deficient (LDLr-KO) mice were fed one of 7 experimental diets for 16 weeks: regular low fat (RL), low trans fat (LT), regular high fat (RH), high trans fat (HT), or an atherogenic diet containing 2% cholesterol, alone (CH) or supplemented with low (CT) or high trans fat (CHT). The extent of lesion development was quantified by en face examination of the dissected aortae. Dietary cholesterol supplementation significantly elevated serum cholesterol levels. Surprisingly, this rise was partially attenuated by the addition of TFAs (CT and CHT) in the diet. Serum triglyceride levels were only elevated in the CHT group. Animals consuming TFAs in the absence of dietary cholesterol developed a small but significantly greater extent of aortic atherosclerotic lesions as compared to control animals (LT > RL and HT > RH). Atherosclerotic lesions were extensive after cholesterol feeding. The addition of TFAs to this atherogenic diet did not advance atherosclerotic development beyond levels observed in the CH group. In summary, consuming TFAs stimulates atherosclerosis, but not beyond the strongly atherogenic effects of dietary cholesterol.
YI-841
MDOC™ (POLYANHYDROGLUCURONIC ACID): NOVEL POTENTIAL HYPOLIPIDEMIC SUBSTANCE
Objective: In humans, SAFAs, especially lauric acid (C12:0), increase HDL-C and apoA-I concentrations, when exchanged iso-energetically for oleic acid, whereas PUFAs and trans MUFAs showed a reduction. Whether these differences are – at least partly – related to differential effects of fatty acids on de novo apoA-I production in the small intestine is currently unknown. Methods: Fatty acids varying in chain length (C8:0, C12:0, C14:0, C16:0, and C18:0), degree of saturation (C18:0, C18:1(n-9), C18:2(n-6), and C18:3(n-3)), or cis/trans configuration (C18:1 9tr, C18:1 11tr, CLA 9c,11tr, and CLA 10c,12tr) were added for 48 hours to fully differentiated CaCo-2 cells, which are a validated model for the small intestine. Fatty acids were exchanged in an isomolar way for oleic acid (C18:1(n-9)). ApoA-I protein concentrations in culture medium were analyzed by an ELISA. Results: All SAFAs, except C18:0, elevated apoA-I concentrations as compared to oleic acid. Although a-linolenic acid (C18:3(n-3)) decreased apoA-I concentrations, no clear relation was found between the degree of saturation and apoA-I production. Surprisingly, elaidic acid (C18:1 9tr) elevated apoA-I production as compared to oleic acid, whereas vaccenic acid (C18:1 11tr), CLA 9c,11tr, and CLA 10c,12tr had no effect. As compared to linoleic acid, CLA 10c,12tr lowered apoA-I production. Conclusions: Differential effects of fatty acids on serum apoA-I concentrations might at least partly be explained by de novo apoA-I production in the small intestine. Especially our finding that SAFAs (C8:0 – C16:0) elevated apoA-I production is suggestive. For trans fatty acids these relationships were less clear.
MDOC™ is micro dispersed derivatives of oxidized cellulose (polyanhydroglucuronic acid). The preliminary data revealed that MDOC™ has mild hypolipidemic and antiinflammatory effects in apoE-deficient mice on chow diet. In this study we wanted to elucidate hypolipidemic mechanism of action of MDOC™ and its effects on cholesterol levels, interleukin-6 levels and vascular cell adhesion molecule levels in both blood and vessel wall in cholesterol fed apoE-deficient mice. Male apoE-/- mice were weaned at 5 weeks of age. Control group (n=8) of mice consumed an atherogenic diet (western type diet) for 4 weeks. Mice in MDOC™ group (n=8) mice consumed the same atherogenic diet supplemented with MDOC™ (50 mg/kg per day) provided by Alltracel Pharmaceuticals for 4 weeks as well. Biochemical analyses of blood cholesterol fractions, determination of bile acid excretion, the fermentation in the large intestine, ELISA analysis of IL-6 and VCAM-1 levels in blood, and the quantification of VCAM-1 expression in aortic sinus were performed. MDOC™ treatment significantly decreased LDL cholesterol and moreover significantly increased HDL cholesterol. ELISA analysis revealed significant decrease of IL-6 levels after MDOC™ treatment. On the contrary VCAM-1 levels remained unchanged in both blood and aortic sinus. Moreover, MDOC™ treatment increased bile acid content in the stool and methane concentration in expired breath as well. This study demonstrates that MDOC™ acting probably as a soluble fiber has hypolipidemic and some anti-inflammatory effects in apoE-deficient mice. However, other studies must be made to elucidate its possible effects on the composition and inflammation in more advanced atherosclerotic lesions.
HIGH BLOOD CHOLESTEROL AWARENESS IN PATIENTS WITH METABOLIC SYNDROME
G.E. Roytberg, N.V. Kondratova, T.I. Ushakova. Russian State Medical University, Moscow, Russia The aim of the study was to estimate the awareness of high blood cholesterol in patients with metabolic syndrome. Methods: 222 persons of local Moscow population without clinical evidence of severe chronic diseases and familial hypercholesterolemia, 129 women and 93 men, aged 30-60 years were screened in “Medicina” Clinic. Survey participants were asked whether they had ever had their blood cholesterol checked and, if so, had a physician ever told them their cholesterol was high. Glucose, total blood cholesterol, HDL cholesterol and triglycerides (TG) were measured in all patients. Metabolic syndrome (MS) was defined by WHO criteria (1999) and required that insulin resistance and two or more abnormalities be present – raised arterial pressure, raised triglycerides, low HDL cholesterol and central obesity. Results: Only 41 patients (18,2%) were aware of their cholesterol level, 23,2% women (n=30) and 11,8% men (n=11). 35,1% of patients had high cholesterol level, 22,1% - high level of TG, 24,3% - low level of HDL cholesterol. In those who were not aware of their cholesterol the prevalence of high cholesterol was 44,0% (38,0% in women and 50,0% in men). The prevalence of metabolic syndrome was 22,5% (n=50). The awareness of total cholesterol in this group of high risk for cardio-vascular diseases was 22%. In 22 patients who didn’t know about their cholesterol, 63% had atherogenic dyslipidemia that requires control. Conclusion: Physicians must pay attention to cholesterol educational programs in patients with metabolic syndrome. YI-843
PATIENTS WITH METABOLIC SYNDROME HAVE HIGHER SERUM GAMMA-GLUTAMYLTRANSFERASE ACTIVITY
E. Karacaglar, H. Bozbas, A. Yildirir, O. Demir, T. Ulus, B. Pirat, S. Eroglu, I. Atar, A. Aydinalp, B. Ozin, H. Muderrisoglu. Department of Cardiology, Baskent University Hospital, Ankara, Turkey Background: Accumulating data indicate that serum gammaglutamyltransferase (GGT) activity represents a true marker of atherosclerotic cardiovascular disease and has prognostic importance. In this study we sought to evaluate serum GGT activity in patients with and without MS.
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
YOUNG INVESTIGATORS
P. Nachtigal 1 , G. Jamborova 1 , N. Pospisilova 1 , K. Pospechova 1 , R. Hyspler 2 , A. Ticha 2 , D. Solichova 2 , C. Andrys 3 , K. Real 4 , V. Semecky 1 . 1 Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic; 2 Department of Metabolic Care and Gerontology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic; 3 Institute of Clinical Immunology and Allergology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic; 4 Alltracel Laboratories, Dublin, Ireland
DIFFERENTIAL EFFECTS OF INDIVIDUAL FATTY ACIDS ON DE NOVO APOA-I PRODUCTION IN DIFFERENTIATED CACO-2 CELLS
S.P. Dullens, R.P. Mensink, J. Plat. Department of Human Biology, Maastricht University, Maastricht, The Netherlands
YI-842 YI-840
223
TRANS FATTY ACIDS STIMULATE ATHEROSCLEROSIS ONLY IN THE ABSENCE OF DIETARY CHOLESTEROL
C.M.C. Dupasquier 1,2,3,4,5 , R.S. McCullough 3,5 , D.P. Blackwood 3,5 , J. Adair 3,5 , J.A. Austria 2,3,5 , G.N. Pierce 1,2,3,4,5 . 1 Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, Manitoba, Canada; 2 Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada; 3 St. Boniface Hospital Research Centre, Winnipeg, Manitoba, Canada; 4 Department of Physiology, Winnipeg, Manitoba, Canada; 5 University of Manitoba, Winnipeg, Manitoba, Canada Epidemiological evidence has associated trans fatty acids (TFAs) in the diet to coronary heart disease. It is assumed that TFAs stimulate atherosclerosis but the only studies to date have shown no effect of TFAs on atherosclerosis. The purpose of this study was to determine the effects of consuming two levels of TFAs, from a commercially hydrogenated vegetable shortening, on atherosclerotic development in the presence or absence of elevated dietary cholesterol. Low-density-lipoprotein receptor deficient (LDLr-KO) mice were fed one of 7 experimental diets for 16 weeks: regular low fat (RL), low trans fat (LT), regular high fat (RH), high trans fat (HT), or an atherogenic diet containing 2% cholesterol, alone (CH) or supplemented with low (CT) or high trans fat (CHT). The extent of lesion development was quantified by en face examination of the dissected aortae. Dietary cholesterol supplementation significantly elevated serum cholesterol levels. Surprisingly, this rise was partially attenuated by the addition of TFAs (CT and CHT) in the diet. Serum triglyceride levels were only elevated in the CHT group. Animals consuming TFAs in the absence of dietary cholesterol developed a small but significantly greater extent of aortic atherosclerotic lesions as compared to control animals (LT > RL and HT > RH). Atherosclerotic lesions were extensive after cholesterol feeding. The addition of TFAs to this atherogenic diet did not advance atherosclerotic development beyond levels observed in the CH group. In summary, consuming TFAs stimulates atherosclerosis, but not beyond the strongly atherogenic effects of dietary cholesterol.
YI-841
MDOC™ (POLYANHYDROGLUCURONIC ACID): NOVEL POTENTIAL HYPOLIPIDEMIC SUBSTANCE
Objective: In humans, SAFAs, especially lauric acid (C12:0), increase HDL-C and apoA-I concentrations, when exchanged iso-energetically for oleic acid, whereas PUFAs and trans MUFAs showed a reduction. Whether these differences are – at least partly – related to differential effects of fatty acids on de novo apoA-I production in the small intestine is currently unknown. Methods: Fatty acids varying in chain length (C8:0, C12:0, C14:0, C16:0, and C18:0), degree of saturation (C18:0, C18:1(n-9), C18:2(n-6), and C18:3(n-3)), or cis/trans configuration (C18:1 9tr, C18:1 11tr, CLA 9c,11tr, and CLA 10c,12tr) were added for 48 hours to fully differentiated CaCo-2 cells, which are a validated model for the small intestine. Fatty acids were exchanged in an isomolar way for oleic acid (C18:1(n-9)). ApoA-I protein concentrations in culture medium were analyzed by an ELISA. Results: All SAFAs, except C18:0, elevated apoA-I concentrations as compared to oleic acid. Although a-linolenic acid (C18:3(n-3)) decreased apoA-I concentrations, no clear relation was found between the degree of saturation and apoA-I production. Surprisingly, elaidic acid (C18:1 9tr) elevated apoA-I production as compared to oleic acid, whereas vaccenic acid (C18:1 11tr), CLA 9c,11tr, and CLA 10c,12tr had no effect. As compared to linoleic acid, CLA 10c,12tr lowered apoA-I production. Conclusions: Differential effects of fatty acids on serum apoA-I concentrations might at least partly be explained by de novo apoA-I production in the small intestine. Especially our finding that SAFAs (C8:0 – C16:0) elevated apoA-I production is suggestive. For trans fatty acids these relationships were less clear.
MDOC™ is micro dispersed derivatives of oxidized cellulose (polyanhydroglucuronic acid). The preliminary data revealed that MDOC™ has mild hypolipidemic and antiinflammatory effects in apoE-deficient mice on chow diet. In this study we wanted to elucidate hypolipidemic mechanism of action of MDOC™ and its effects on cholesterol levels, interleukin-6 levels and vascular cell adhesion molecule levels in both blood and vessel wall in cholesterol fed apoE-deficient mice. Male apoE-/- mice were weaned at 5 weeks of age. Control group (n=8) of mice consumed an atherogenic diet (western type diet) for 4 weeks. Mice in MDOC™ group (n=8) mice consumed the same atherogenic diet supplemented with MDOC™ (50 mg/kg per day) provided by Alltracel Pharmaceuticals for 4 weeks as well. Biochemical analyses of blood cholesterol fractions, determination of bile acid excretion, the fermentation in the large intestine, ELISA analysis of IL-6 and VCAM-1 levels in blood, and the quantification of VCAM-1 expression in aortic sinus were performed. MDOC™ treatment significantly decreased LDL cholesterol and moreover significantly increased HDL cholesterol. ELISA analysis revealed significant decrease of IL-6 levels after MDOC™ treatment. On the contrary VCAM-1 levels remained unchanged in both blood and aortic sinus. Moreover, MDOC™ treatment increased bile acid content in the stool and methane concentration in expired breath as well. This study demonstrates that MDOC™ acting probably as a soluble fiber has hypolipidemic and some anti-inflammatory effects in apoE-deficient mice. However, other studies must be made to elucidate its possible effects on the composition and inflammation in more advanced atherosclerotic lesions.
HIGH BLOOD CHOLESTEROL AWARENESS IN PATIENTS WITH METABOLIC SYNDROME
G.E. Roytberg, N.V. Kondratova, T.I. Ushakova. Russian State Medical University, Moscow, Russia The aim of the study was to estimate the awareness of high blood cholesterol in patients with metabolic syndrome. Methods: 222 persons of local Moscow population without clinical evidence of severe chronic diseases and familial hypercholesterolemia, 129 women and 93 men, aged 30-60 years were screened in “Medicina” Clinic. Survey participants were asked whether they had ever had their blood cholesterol checked and, if so, had a physician ever told them their cholesterol was high. Glucose, total blood cholesterol, HDL cholesterol and triglycerides (TG) were measured in all patients. Metabolic syndrome (MS) was defined by WHO criteria (1999) and required that insulin resistance and two or more abnormalities be present – raised arterial pressure, raised triglycerides, low HDL cholesterol and central obesity. Results: Only 41 patients (18,2%) were aware of their cholesterol level, 23,2% women (n=30) and 11,8% men (n=11). 35,1% of patients had high cholesterol level, 22,1% - high level of TG, 24,3% - low level of HDL cholesterol. In those who were not aware of their cholesterol the prevalence of high cholesterol was 44,0% (38,0% in women and 50,0% in men). The prevalence of metabolic syndrome was 22,5% (n=50). The awareness of total cholesterol in this group of high risk for cardio-vascular diseases was 22%. In 22 patients who didn’t know about their cholesterol, 63% had atherogenic dyslipidemia that requires control. Conclusion: Physicians must pay attention to cholesterol educational programs in patients with metabolic syndrome. YI-843
PATIENTS WITH METABOLIC SYNDROME HAVE HIGHER SERUM GAMMA-GLUTAMYLTRANSFERASE ACTIVITY
E. Karacaglar, H. Bozbas, A. Yildirir, O. Demir, T. Ulus, B. Pirat, S. Eroglu, I. Atar, A. Aydinalp, B. Ozin, H. Muderrisoglu. Department of Cardiology, Baskent University Hospital, Ankara, Turkey Background: Accumulating data indicate that serum gammaglutamyltransferase (GGT) activity represents a true marker of atherosclerotic cardiovascular disease and has prognostic importance. In this study we sought to evaluate serum GGT activity in patients with and without MS.
76th Congress of the European Atherosclerosis Society, June 10–13, 2007, Helsinki, Finland
YOUNG INVESTIGATORS
P. Nachtigal 1 , G. Jamborova 1 , N. Pospisilova 1 , K. Pospechova 1 , R. Hyspler 2 , A. Ticha 2 , D. Solichova 2 , C. Andrys 3 , K. Real 4 , V. Semecky 1 . 1 Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic; 2 Department of Metabolic Care and Gerontology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic; 3 Institute of Clinical Immunology and Allergology, Charles University Medical School and Teaching Hospital, Hradec Kralove, Czech Republic; 4 Alltracel Laboratories, Dublin, Ireland
DIFFERENTIAL EFFECTS OF INDIVIDUAL FATTY ACIDS ON DE NOVO APOA-I PRODUCTION IN DIFFERENTIATED CACO-2 CELLS
S.P. Dullens, R.P. Mensink, J. Plat. Department of Human Biology, Maastricht University, Maastricht, The Netherlands
YI-842 YI-840
223