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2P-0473 Effect of anthocyanins from chokeberry (Aronia melanocarpa) on blood pressure, inflammatory mediators and cell adhesion molecules in patients with a history of myocardial infarction (MI)
Tuesday September 30, 2003: Poster Session Adhesion molecules Methods: twenty-five rabbits were divided into three groups: normal diet group, high-cholesterol group, Irbesartan group (50mg/kg/day). The later two groups received 1% cholesterol diet for 12 weeks to establish the early atherosclerosis model. Blood samples were collected for cholesterol assessment and angiotensin concentrations; the levels of expression of VCAM-1 mRNA were evaluated by RT-PCR and Northern Blot. Results: There is no difference between the two high-cholesterol groups, although the cholesterol level of these groups are much higher than the normal-diet group; Rabbits received Irbesartan showed reduced intimal thickness and the ratio of aotic intimal thickness to medial thickness compared with placebo-treated group (p<0.05). Irbesartan administration for 12 weeks caused a down-regulation in arterial expression of VCAM-1 normalized to GAPDH (p<0.05). Conclusion: Chronic Irbesartan treatment ameliorated the severity of the early atherosclerosis lesions, possibly because of the suppression of VCAM-1 mRNA expression. 2P-0470
Influence of hypercholesterolemia and long-term HMG-CoA reductase inhibitors treatment on sE-selectin and sICAM-1 levels in hyperlipidemic patients without any other risk factor and CAD
N.C. Panagoulis 1 , S.A. Perpinia 2 , A.N. Michelakakis 1 , I.A. Goudinakis 1 , K.P. Charbis 2 , A.A. Zacharoulis 1 . 1 Cardiology Department, Athens General Hospital, Athens; 2 Cardiology Department, Polycliniki General Hospital, Athens, Greece
2P-0471
Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans
H. Koyama, T. Maeno, S. Fukumoto, T. Shoji, H. Yokoyama, S. Fujiwara, M. Emoto, H. Tahara, S. Tanaka, A. Shioi, Y. Nishizawa. Osaka City University Graduate School of Medicine, Osaka, Japan Recent animal experiments reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in human subjects. Unrelated subjects (n=517; 235 males, 282 females), including 187 type 2 diabetics, 184 with hypertension and 366 with hyperlipidemia, were enrolled in the study. Platelet P-selectin expression was determined by whole blood flow cytometry. Arterial wall thickness (intima-media thickness: IMT) was determined by carotid ultrasound. P-selectin positive platelets was significantly (p<0.0001) correlated with carotid IMT (r=0.339). Multiple regression analyses showed that the association of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. P-selectin positive platelets was higher in subjects with carotid plaque than those without it (median 1.72 vs 0.80, p<0.0001, Mann-Whitney U-test). P-selectin was independently associated with the presence of carotid plaque analyzed by multiple logistic regression analysis (OR 3.37 with 10 point increase in P-selectin adjusted with age, gender, smoking index, body mass index,
systolic blood pressure, HbA1c, non-HDL and HDL cholesterol). Finally, P-selectin-positive platelets was significantly (p<0.0001) higher in diabetic (median 1.42 vs 0.70) or hypertensive (median 1.01 vs 0.71) subjects. In simple regression analyses, P-selectin positive platelets were significantly associated with age (r=0.260), body mass index (r=0.114), systolic (r=0.177) and diastolic blood pressure (r=0.147), HbA1c (r=0.390), and HDL-cholesterol (r=-0.150). Together with recently reported basic observations, platelet Pselectin is independently associated with carotid atherosclerosis in human subjects, and could be regarded as an independent risk factor for progression of atherosclerosis. 2P-0472
Increased expression of monocyte CD11a/CD18 and its ligand ICAM-1 in patients with initial atherosclerotic coronary stenosis
A. Kawamura, S. Miura, M. Fujino, T. Murayama, H. Nishikawa, Y. Matsuo, S. Tomita, Y. Tsuchiya, K. Matsuo, E. Tsuji, K. Saku. Department of Cardiology, Fukuoka University, Fukuoka City, Japan Objectives: Cell adhesion molecules have been implicated in leukocyte adhesion to endothelial cells and play a role in atherosclerosis, which is a frequent cause of morbidity and mortality in patients with coronary artery disease (CAD) or hemodialysis (HD). Therefore, we measured leukocyte adhesion molecules in patients with CAD or HD. Methods: The expression of leukocyte (neutrophil, monocyte and lymphocyte) surface CD11a, CD11b, CD18, intracellular adhesion molecule-1 (ICAM-1), very late antigen-4a (VLA-4 a) and L-selectin was investigated by flow cytometry in 20 patients who had been initially diagnosed with CAD (age: 64±9 years), 20 undergoing HD (55±11 years) and 20 without CAD (CONT) (61±9 years). Results: Monocyte surface expression of CD11a and ICAM-1 in the CAD group was significantly higher than those in the CONT group. Interestingly, CD11a and ICAM-1 expression in the HD group were significantly lower than those in the CAD group. In addition, when we analyzed 15 CAD patients with re-stenosed coronary vessels (66±13 years), these patients showed monocyte CD11a and ICAM-1 expression levels similar to those in the CONT group. Monocyte L-selectin was also increased in the CAD group. Conclusion: Since CD11a and CD18 are expressed on the cell surface as a heterodimer and ICAM-1 is a ligand for CD11a/CD18, this increased expression of CD11a and ICAM-1 may affect the development of initial atherosclerotic coronary stenosis. 2P-0473
Effect of anthocyanins from chokeberry (Aronia melanocarpa) on blood pressure, inflammatory mediators and cell adhesion molecules in patients with a history of myocardial infarction (MI)
M. Naruszewicz 1 , M. Daniewski 2 , I. Łaniewska 2 , W. Pikto-Pietkiewicz 2 , B. Millo 1 , D. Zapolska-Downar 1 . 1 Pomeranian Medical University, Department of Clinical Biochemistry, Szczecin; 2 The Medical University of Warsaw, II Cardiology Clinic, Poland Recent studies have shown, that chronic flavonoids treatment improves vascular function and cardiovascular remodeling by decreasing superoxide anion production as well as by increasing NO realize from endothelial cells and platelet. A progressive decrease in systolic blood pressure and reduction of low-density lipoprotein oxidation (Ox-LDL) has also been reported. However, none of these studies were done in patient with coronary artery disease. We performed a double-blind placebo controlled parallel trial in which 26 patients after MI were allocated to recive either (3x100 mg/d) of chokeberry anthocyanins (13 patients) or matched placebo (13 patients) for 6 weeks. Other medications remained unchanged during the study period. A significant decreases (two factor ANOVA) in systolic p < 0.001 and diastolic p < 0.005 blood pressure were recorded in the anthocyanins group. In addition, anthocyanins decreases the plasma levels of IL-6 by 27%, ox-LDL by 26%, CRP by 18% and VCAM by 17% in comparison with baseline. No such changes were observed in the placebo group. We also measured the production of reactive oxygen species (ROS) by resting or stimulated by HUVEC cells (in vitro) in the presence or absence of chokeberry anthocyanins. A marked inhibitory effects of anthocyanins on ROS production in TNFα activated cells was noted. Altogether, these results suggest that anthocyanins may reduce oxidative stress and inhibit cytokine-induced inflammatory responses in patients with MI.
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
TUESDAY
Background: The expression of ICAM-1 and E-selectin, on surface of endothelium is important step in initiation and progression of atherosclerosis. This study was performed to determine the effects of an HMG-CoA inhibitor on sICAM-l and sE-selectin in hypercholesterolemic subjects (HCh) with no other risk factors (RF) or evidence of atherosclerosis. Methods: 34 healthy HCh patients (21 males,13 females, aged 49.4 ± 5.2 y), without diabetes melitus, hypertension or CAD, were enrolled in this study, receiving Atorvastatin (A) 40 mg/d for 24 months. Plasma levels of sICAM-1, and sE-selectin were determined before and after 12 and 24 months. The same parameters were measured in19 subjects (C) with normal cholesterol levels, matched for sex and age. Results: HCh had sICAM-1 basal values higher than C, (272 ± 7 ng/ml vs 176 ±9 ng/ml, P < 0.001). sE-selectin basal values were 65 ± 8 vs 57 ±4 ng/ml (NS). No correlation was observed at baseline between HCh, sICAM-1 and cholesterol levels. 24 months later the A treatment significantly reduced sICAM-1 (from 272 ± 7 ng/ml to 186 ± 6 ng/ml, p=0.001) and LDL-c (268 ± 17 ng/ml to 118 ± 10 ng/ml p=0.001), while sE-selectin reduced but remained statistical unchanged (65 ± 8 ng/ml to 56 ± 4 ng/ml p=0.02). Conclusions: The results suggest that HCh patients have higher sICAM-1 levels, and A decreases sICAM-1 levels in HCh without CAD and other RF. These effects may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.
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Influence of hypercholesterolemia and long-term HMG-CoA reductase inhibitors treatment on sE-selectin and sICAM-1 levels in hyperlipidemic patients without any other risk factor and CAD
N.C. Panagoulis 1 , S.A. Perpinia 2 , A.N. Michelakakis 1 , I.A. Goudinakis 1 , K.P. Charbis 2 , A.A. Zacharoulis 1 . 1 Cardiology Department, Athens General Hospital, Athens; 2 Cardiology Department, Polycliniki General Hospital, Athens, Greece
2P-0471
Platelet P-selectin expression is associated with atherosclerotic wall thickness in carotid artery in humans
H. Koyama, T. Maeno, S. Fukumoto, T. Shoji, H. Yokoyama, S. Fujiwara, M. Emoto, H. Tahara, S. Tanaka, A. Shioi, Y. Nishizawa. Osaka City University Graduate School of Medicine, Osaka, Japan Recent animal experiments reveal important roles of platelet P-selectin on progression of atherosclerosis. In the present study, we examine the relation between platelet P-selectin expression and atherosclerotic parameters in human subjects. Unrelated subjects (n=517; 235 males, 282 females), including 187 type 2 diabetics, 184 with hypertension and 366 with hyperlipidemia, were enrolled in the study. Platelet P-selectin expression was determined by whole blood flow cytometry. Arterial wall thickness (intima-media thickness: IMT) was determined by carotid ultrasound. P-selectin positive platelets was significantly (p<0.0001) correlated with carotid IMT (r=0.339). Multiple regression analyses showed that the association of P-selectin-positive platelets with carotid IMT was independent of other clinical factors. P-selectin positive platelets was higher in subjects with carotid plaque than those without it (median 1.72 vs 0.80, p<0.0001, Mann-Whitney U-test). P-selectin was independently associated with the presence of carotid plaque analyzed by multiple logistic regression analysis (OR 3.37 with 10 point increase in P-selectin adjusted with age, gender, smoking index, body mass index,
systolic blood pressure, HbA1c, non-HDL and HDL cholesterol). Finally, P-selectin-positive platelets was significantly (p<0.0001) higher in diabetic (median 1.42 vs 0.70) or hypertensive (median 1.01 vs 0.71) subjects. In simple regression analyses, P-selectin positive platelets were significantly associated with age (r=0.260), body mass index (r=0.114), systolic (r=0.177) and diastolic blood pressure (r=0.147), HbA1c (r=0.390), and HDL-cholesterol (r=-0.150). Together with recently reported basic observations, platelet Pselectin is independently associated with carotid atherosclerosis in human subjects, and could be regarded as an independent risk factor for progression of atherosclerosis. 2P-0472
Increased expression of monocyte CD11a/CD18 and its ligand ICAM-1 in patients with initial atherosclerotic coronary stenosis
A. Kawamura, S. Miura, M. Fujino, T. Murayama, H. Nishikawa, Y. Matsuo, S. Tomita, Y. Tsuchiya, K. Matsuo, E. Tsuji, K. Saku. Department of Cardiology, Fukuoka University, Fukuoka City, Japan Objectives: Cell adhesion molecules have been implicated in leukocyte adhesion to endothelial cells and play a role in atherosclerosis, which is a frequent cause of morbidity and mortality in patients with coronary artery disease (CAD) or hemodialysis (HD). Therefore, we measured leukocyte adhesion molecules in patients with CAD or HD. Methods: The expression of leukocyte (neutrophil, monocyte and lymphocyte) surface CD11a, CD11b, CD18, intracellular adhesion molecule-1 (ICAM-1), very late antigen-4a (VLA-4 a) and L-selectin was investigated by flow cytometry in 20 patients who had been initially diagnosed with CAD (age: 64±9 years), 20 undergoing HD (55±11 years) and 20 without CAD (CONT) (61±9 years). Results: Monocyte surface expression of CD11a and ICAM-1 in the CAD group was significantly higher than those in the CONT group. Interestingly, CD11a and ICAM-1 expression in the HD group were significantly lower than those in the CAD group. In addition, when we analyzed 15 CAD patients with re-stenosed coronary vessels (66±13 years), these patients showed monocyte CD11a and ICAM-1 expression levels similar to those in the CONT group. Monocyte L-selectin was also increased in the CAD group. Conclusion: Since CD11a and CD18 are expressed on the cell surface as a heterodimer and ICAM-1 is a ligand for CD11a/CD18, this increased expression of CD11a and ICAM-1 may affect the development of initial atherosclerotic coronary stenosis. 2P-0473
Effect of anthocyanins from chokeberry (Aronia melanocarpa) on blood pressure, inflammatory mediators and cell adhesion molecules in patients with a history of myocardial infarction (MI)
M. Naruszewicz 1 , M. Daniewski 2 , I. Łaniewska 2 , W. Pikto-Pietkiewicz 2 , B. Millo 1 , D. Zapolska-Downar 1 . 1 Pomeranian Medical University, Department of Clinical Biochemistry, Szczecin; 2 The Medical University of Warsaw, II Cardiology Clinic, Poland Recent studies have shown, that chronic flavonoids treatment improves vascular function and cardiovascular remodeling by decreasing superoxide anion production as well as by increasing NO realize from endothelial cells and platelet. A progressive decrease in systolic blood pressure and reduction of low-density lipoprotein oxidation (Ox-LDL) has also been reported. However, none of these studies were done in patient with coronary artery disease. We performed a double-blind placebo controlled parallel trial in which 26 patients after MI were allocated to recive either (3x100 mg/d) of chokeberry anthocyanins (13 patients) or matched placebo (13 patients) for 6 weeks. Other medications remained unchanged during the study period. A significant decreases (two factor ANOVA) in systolic p < 0.001 and diastolic p < 0.005 blood pressure were recorded in the anthocyanins group. In addition, anthocyanins decreases the plasma levels of IL-6 by 27%, ox-LDL by 26%, CRP by 18% and VCAM by 17% in comparison with baseline. No such changes were observed in the placebo group. We also measured the production of reactive oxygen species (ROS) by resting or stimulated by HUVEC cells (in vitro) in the presence or absence of chokeberry anthocyanins. A marked inhibitory effects of anthocyanins on ROS production in TNFα activated cells was noted. Altogether, these results suggest that anthocyanins may reduce oxidative stress and inhibit cytokine-induced inflammatory responses in patients with MI.
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
TUESDAY
Background: The expression of ICAM-1 and E-selectin, on surface of endothelium is important step in initiation and progression of atherosclerosis. This study was performed to determine the effects of an HMG-CoA inhibitor on sICAM-l and sE-selectin in hypercholesterolemic subjects (HCh) with no other risk factors (RF) or evidence of atherosclerosis. Methods: 34 healthy HCh patients (21 males,13 females, aged 49.4 ± 5.2 y), without diabetes melitus, hypertension or CAD, were enrolled in this study, receiving Atorvastatin (A) 40 mg/d for 24 months. Plasma levels of sICAM-1, and sE-selectin were determined before and after 12 and 24 months. The same parameters were measured in19 subjects (C) with normal cholesterol levels, matched for sex and age. Results: HCh had sICAM-1 basal values higher than C, (272 ± 7 ng/ml vs 176 ±9 ng/ml, P < 0.001). sE-selectin basal values were 65 ± 8 vs 57 ±4 ng/ml (NS). No correlation was observed at baseline between HCh, sICAM-1 and cholesterol levels. 24 months later the A treatment significantly reduced sICAM-1 (from 272 ± 7 ng/ml to 186 ± 6 ng/ml, p=0.001) and LDL-c (268 ± 17 ng/ml to 118 ± 10 ng/ml p=0.001), while sE-selectin reduced but remained statistical unchanged (65 ± 8 ng/ml to 56 ± 4 ng/ml p=0.02). Conclusions: The results suggest that HCh patients have higher sICAM-1 levels, and A decreases sICAM-1 levels in HCh without CAD and other RF. These effects may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.
143