- Email: [email protected]
OB) mice
138
Kipshidze
purpose of our study was to assess the effects of cupressus sempervirens cone extract (CSE) on the lipid profile in Wistar rats. Materials and Methods: The animals were divided in two groups. Group I (30 animals) received CSE for 24 weeks and group II (30 animals) served as a control group. Serum lipid parameters, muscle and liver enzymes, red and white blood count, platelets, and serum concentrations of uric acid and creatinine were determined at baseline and at weeks, 12, 18, and 24 of the study. Results: The administration of the extract resulted in a substantial decrease of serum total cholesterol, which was significant even after 6 weeks of treatment. Moreover, these animals exhibited lower total cholesterol levels compared to controls after initiation of treatment (p <0.001) during the study period. Although the administration of the extract led to a substantial reduction in serum triglycerides (p<0.05), no significant differences in triglyceride levels were observed between CSE animals and controls during the study period. No significant changes in HDL-cholesterol as well as in the other parameters occurred in both groups. Conclusion: The administration of CSE has an important lipid-lowering effect in Wistar rats. Although these results cannot be extrapolated in humans this extract might be potentially interesting in the treatment of dyslipidemia.
STABILIZATION EFFECTS •3-5] PLAQUE ATORVA STATINE
OF THE
N. Kipshidze, N. Kakauridze. Research Institute of Clinical and
Experimental Therapy, Tbilisi, Georgia The aim of this work is to study of carotid artery plaque stabilization by atorvastatine influence on the hyperlipidemia. 12 patients (44~5 years) with hyperlipidemia (total cholesterol (C) level>200mg/dl, LDL-C>130mg/dl, HDL-C<35mg/dl, Trigylcerides (TG)>200mg/dl) had been receiving atorvastatine therapy at the 40mg for 1 year and in whom the presence of an atherosclerotic plaque in the carotid artery had been confirmed by ultrasonography. Blood samples were collected for each person after both 12 hour fasting. Non-hemolised serum underwent the following tests: TC, TG enzimatically and HDL-C after precipitation of VLDL and LDL using BIOLABO, France Kits on the spectrophotometer "Jaenvay-6400". LDL-C was calculated according to Friedwald. Blood Fibrinogen was performed by weithing method (test- "Bio-Fibri" France). Lipids and fibrinogen were measured before treatment and a 3-month intervals after the start of treatment. In each patient, the largest plaque lesion up to bifurcation of the internal and external carotide arteries was evaluated using Doppler echographic imaging system at the beginning of the study and at the study and changes in the plaque composition were determined. The results indicate that atorvastatine therapy have a beneficial influence on the lipid metabolism and induces plaque stability. Plaque stabilization is brought about by inhibition of lipid core regression and thickening of the fragile fibrouse matrix.
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ARTERIAL WALL STIFFNESS IS ASSOCIATED W I T H PERIPHERAL CIRCULATIONS IN PATIENTS W I T H TYPE 2 DIABETES
A. Kizu, H. Koyama, S. Tanaka, T. Maeno, M. Komatsu, M. Emoto, H. Yokoyama, T. Shoji, M. Inaba, Y. Nishizawa. Osaka City University
Graduate School of Medicine, Osaka, Japan Background: Transcutaneous oxygen tension (TcPO2) is a noninvasive and quantitative method to assess peripheral circulations. The purpose of this study was to evaluate the relationship between TcPO2 and the level of atherosclerosis (wall thickness and arterial stiffness) in patients with type 2 diabetes. Subjects: Sixty-seven asymptomatic patients (male 25, female 42) with type 2 diabetes participated to the study. Mean age was 57±12.0 (SE) years old and mean HbAlc was 8.2±7.3%. Methods: TcPO2 was monitored during treadmill-exercise on 12% slope with 2.4km/h velocity for 5 minutes. The TcPO2 index was expressed as percentage of post-exercise TcPO2 adjusted with pre-exercise TcPO2. Arterial intimal media thickness (IMT), a wall thickness parameter, and stiffness parameter beta (stiffness beta), an index of arterial stiffening, were measured by arterial ultrasound. Results: By simple regression analyses, TcPO2 index was negatively correlated with stiffness beta of femoral artery (r--0.295, P-0.041), but not with that of carotid artery or IMT. Multiple regression analyses showed that association of stiffness beta of femoral artery with TcPO2 index was independent on the other risk factors including age, duration of diabetes, smoking index and IMT of femoral artery (R2-0.170, P<0.003). Conclusion: Stiffness femoral artery determines peripheral circulation in type 2 diabetic patients without ischemic symptoms in lower limb. ~3-8] SUPPRESSION OF INFLAMMATION MARKERS AND CELLULAR IMMUNE FUNCTION IN OBESE (OB/OB) MICE Z. Berke, M. Kierrulf, N. Oakes, E. Hurt-Camejo. AstraZeneca R&D,
Molndal, Sweden Obesity and insulin resistance in humans are associated with subclinical inflammation, which may increase the risk for atherosclerosis. In ob/ob mice a mutation in the leptin gene causes obesity, the mice gaining weight up to three times more than normal mice. In the present study, we analysed spleen and peritoneal cell activation in ob/ob mice. Peritoneal macrophages of ob/ob mice had significantly lower expression of activation markers CD 1l b, CD40, CD86 and scavenger receptor type A, when compared with lean or C57B1/6 (wt) mice. Peritoneal B cells of ob/ob mice had a reduced expression of activation markers CD54 and CD86. Moreover, the proportion of CD1 lb(dim) lymphocytes, corresponding to B-1 cells, was reduced in ob/ob mice. When spleen cells were stimulated with anti-CD3+anti-CD28, PHA or PMA+ionomycin the production of IL-2, IL-6, TNF-c~, and IFN-y was reduced in ob/ob mice as compared to wt. No difference in proliferative response to these stimuli was observed between ob/ob and wt mice. Taken together these results show a clear suppression of inflammation markers and cellular immune function in ob/ob mice. The relevance of the ob/ob mouse model for studies of metabolic disorders in relation to inflammation and atherosclerosis is questioned.
OXIDIZED LDL RECEPTORS AND ATHEROSCLEROSIS ~]
T. Kita. Kyoto University, Department of Geriatric Medicine, Kyoto, Japan One of the critical events in the early stage of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of athrosclerosis, it was found that localized attachment of circulating monocytes to arterial endothelial ceils appears to precede the formation of foam ceils. It has been suggested that monocyte recruitment into early lesions is depend upon the endotherial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as VCAM-I,ICAM-1 and P-selecin, those can support the adhesion of monocytes and lymphocytes. Moreover oxidized LDL, lysophosphatidyl-choline and oxidized fatty acids induce the expression of not only these adhesion molecules but also scagenger receptors, such as CD-36, SR-A and LOX-1.Recently we isolated and characterized the novel receptors for oxidized LDL, named LOX-1 and SR-PSOX. The expression of LOX-1 is found on endotherial cells, smooth muscle cells and macrophages. Whereas SR-PSOX expresses on macrophages. We address in this paper on the significance of hyperlipidemia, especially oxidized LDL and its receptors in terms of atherogenesis.
CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) CONCENTRATION INFLUENCES PROGRESSION OF ATHEROSCLEROSIS AND RESPONSE TO PRAVASTATIN TREATMENT; THE REGRESS STUDY
A.H.E.M. Klerkx 1, G.J. De Grooth 1, A.H. Zwinderman 1'2, J.W. Jukema2, J.A. Kuivenhoven1, J.J.P. Kastelein 1. IAcademic Medical Center, University
of Amsterdam," 2Leiden University Medical Center, The Netherlands Background: The B1 allele of the CETP TaqIB polymorphism is associated with lower HI)L-C, higher progression of coronary artery disease (CAD) and better response to pravastatin in men with proven CAD (REGRESS). We now investigated whether differences in CETP concentration among CETP genotypes could explain these associations. Methods: Plasma CETP concentrations at baseline and after 2-year treatment with pravastatin or placebo were measured in 674 REGRESS patients. After segregation into baseline CETP quartiles (CETP2.21 mg/1), correlations with lipid parameters and progression of CAD (changes in mean segment diameter (MSD) and minimum obstruction diameter (MOD)) were studied.
73rd EAS Congress
Kipshidze
purpose of our study was to assess the effects of cupressus sempervirens cone extract (CSE) on the lipid profile in Wistar rats. Materials and Methods: The animals were divided in two groups. Group I (30 animals) received CSE for 24 weeks and group II (30 animals) served as a control group. Serum lipid parameters, muscle and liver enzymes, red and white blood count, platelets, and serum concentrations of uric acid and creatinine were determined at baseline and at weeks, 12, 18, and 24 of the study. Results: The administration of the extract resulted in a substantial decrease of serum total cholesterol, which was significant even after 6 weeks of treatment. Moreover, these animals exhibited lower total cholesterol levels compared to controls after initiation of treatment (p <0.001) during the study period. Although the administration of the extract led to a substantial reduction in serum triglycerides (p<0.05), no significant differences in triglyceride levels were observed between CSE animals and controls during the study period. No significant changes in HDL-cholesterol as well as in the other parameters occurred in both groups. Conclusion: The administration of CSE has an important lipid-lowering effect in Wistar rats. Although these results cannot be extrapolated in humans this extract might be potentially interesting in the treatment of dyslipidemia.
STABILIZATION EFFECTS •3-5] PLAQUE ATORVA STATINE
OF THE
N. Kipshidze, N. Kakauridze. Research Institute of Clinical and
Experimental Therapy, Tbilisi, Georgia The aim of this work is to study of carotid artery plaque stabilization by atorvastatine influence on the hyperlipidemia. 12 patients (44~5 years) with hyperlipidemia (total cholesterol (C) level>200mg/dl, LDL-C>130mg/dl, HDL-C<35mg/dl, Trigylcerides (TG)>200mg/dl) had been receiving atorvastatine therapy at the 40mg for 1 year and in whom the presence of an atherosclerotic plaque in the carotid artery had been confirmed by ultrasonography. Blood samples were collected for each person after both 12 hour fasting. Non-hemolised serum underwent the following tests: TC, TG enzimatically and HDL-C after precipitation of VLDL and LDL using BIOLABO, France Kits on the spectrophotometer "Jaenvay-6400". LDL-C was calculated according to Friedwald. Blood Fibrinogen was performed by weithing method (test- "Bio-Fibri" France). Lipids and fibrinogen were measured before treatment and a 3-month intervals after the start of treatment. In each patient, the largest plaque lesion up to bifurcation of the internal and external carotide arteries was evaluated using Doppler echographic imaging system at the beginning of the study and at the study and changes in the plaque composition were determined. The results indicate that atorvastatine therapy have a beneficial influence on the lipid metabolism and induces plaque stability. Plaque stabilization is brought about by inhibition of lipid core regression and thickening of the fragile fibrouse matrix.
~]
•]
ARTERIAL WALL STIFFNESS IS ASSOCIATED W I T H PERIPHERAL CIRCULATIONS IN PATIENTS W I T H TYPE 2 DIABETES
A. Kizu, H. Koyama, S. Tanaka, T. Maeno, M. Komatsu, M. Emoto, H. Yokoyama, T. Shoji, M. Inaba, Y. Nishizawa. Osaka City University
Graduate School of Medicine, Osaka, Japan Background: Transcutaneous oxygen tension (TcPO2) is a noninvasive and quantitative method to assess peripheral circulations. The purpose of this study was to evaluate the relationship between TcPO2 and the level of atherosclerosis (wall thickness and arterial stiffness) in patients with type 2 diabetes. Subjects: Sixty-seven asymptomatic patients (male 25, female 42) with type 2 diabetes participated to the study. Mean age was 57±12.0 (SE) years old and mean HbAlc was 8.2±7.3%. Methods: TcPO2 was monitored during treadmill-exercise on 12% slope with 2.4km/h velocity for 5 minutes. The TcPO2 index was expressed as percentage of post-exercise TcPO2 adjusted with pre-exercise TcPO2. Arterial intimal media thickness (IMT), a wall thickness parameter, and stiffness parameter beta (stiffness beta), an index of arterial stiffening, were measured by arterial ultrasound. Results: By simple regression analyses, TcPO2 index was negatively correlated with stiffness beta of femoral artery (r--0.295, P-0.041), but not with that of carotid artery or IMT. Multiple regression analyses showed that association of stiffness beta of femoral artery with TcPO2 index was independent on the other risk factors including age, duration of diabetes, smoking index and IMT of femoral artery (R2-0.170, P<0.003). Conclusion: Stiffness femoral artery determines peripheral circulation in type 2 diabetic patients without ischemic symptoms in lower limb. ~3-8] SUPPRESSION OF INFLAMMATION MARKERS AND CELLULAR IMMUNE FUNCTION IN OBESE (OB/OB) MICE Z. Berke, M. Kierrulf, N. Oakes, E. Hurt-Camejo. AstraZeneca R&D,
Molndal, Sweden Obesity and insulin resistance in humans are associated with subclinical inflammation, which may increase the risk for atherosclerosis. In ob/ob mice a mutation in the leptin gene causes obesity, the mice gaining weight up to three times more than normal mice. In the present study, we analysed spleen and peritoneal cell activation in ob/ob mice. Peritoneal macrophages of ob/ob mice had significantly lower expression of activation markers CD 1l b, CD40, CD86 and scavenger receptor type A, when compared with lean or C57B1/6 (wt) mice. Peritoneal B cells of ob/ob mice had a reduced expression of activation markers CD54 and CD86. Moreover, the proportion of CD1 lb(dim) lymphocytes, corresponding to B-1 cells, was reduced in ob/ob mice. When spleen cells were stimulated with anti-CD3+anti-CD28, PHA or PMA+ionomycin the production of IL-2, IL-6, TNF-c~, and IFN-y was reduced in ob/ob mice as compared to wt. No difference in proliferative response to these stimuli was observed between ob/ob and wt mice. Taken together these results show a clear suppression of inflammation markers and cellular immune function in ob/ob mice. The relevance of the ob/ob mouse model for studies of metabolic disorders in relation to inflammation and atherosclerosis is questioned.
OXIDIZED LDL RECEPTORS AND ATHEROSCLEROSIS ~]
T. Kita. Kyoto University, Department of Geriatric Medicine, Kyoto, Japan One of the critical events in the early stage of atherosclerosis is the focal accumulation of lipid-laden foam cells derived from macrophages. In various cholesterol-fed animal models of athrosclerosis, it was found that localized attachment of circulating monocytes to arterial endothelial ceils appears to precede the formation of foam ceils. It has been suggested that monocyte recruitment into early lesions is depend upon the endotherial adhesiveness for monocytes and lymphocytes. In vivo and in vitro experiments have identified molecules, such as VCAM-I,ICAM-1 and P-selecin, those can support the adhesion of monocytes and lymphocytes. Moreover oxidized LDL, lysophosphatidyl-choline and oxidized fatty acids induce the expression of not only these adhesion molecules but also scagenger receptors, such as CD-36, SR-A and LOX-1.Recently we isolated and characterized the novel receptors for oxidized LDL, named LOX-1 and SR-PSOX. The expression of LOX-1 is found on endotherial cells, smooth muscle cells and macrophages. Whereas SR-PSOX expresses on macrophages. We address in this paper on the significance of hyperlipidemia, especially oxidized LDL and its receptors in terms of atherogenesis.
CHOLESTERYL ESTER TRANSFER PROTEIN (CETP) CONCENTRATION INFLUENCES PROGRESSION OF ATHEROSCLEROSIS AND RESPONSE TO PRAVASTATIN TREATMENT; THE REGRESS STUDY
A.H.E.M. Klerkx 1, G.J. De Grooth 1, A.H. Zwinderman 1'2, J.W. Jukema2, J.A. Kuivenhoven1, J.J.P. Kastelein 1. IAcademic Medical Center, University
of Amsterdam," 2Leiden University Medical Center, The Netherlands Background: The B1 allele of the CETP TaqIB polymorphism is associated with lower HI)L-C, higher progression of coronary artery disease (CAD) and better response to pravastatin in men with proven CAD (REGRESS). We now investigated whether differences in CETP concentration among CETP genotypes could explain these associations. Methods: Plasma CETP concentrations at baseline and after 2-year treatment with pravastatin or placebo were measured in 674 REGRESS patients. After segregation into baseline CETP quartiles (CETP
73rd EAS Congress