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2P-0466 Role of soluble adhesion molecules in the pathogenesis of hypertensive vascular lesions in obesity
142 2P-0465
Tuesday September 30, 2003: Poster Session Adhesion molecules Adenovirus-mediated overexpression of superoxide dismutase attenuates VCAM-1 and ICAM-1 expression in TNF-α-treated human aortic endothelial cells
Y.L. Chen 1 , S.J. Lin 2 , Y.Y. Hung 1 , S.K. Shyue 3 , Y.H. Chen 4 , J.W. Chen 2 . 1 Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University; 2 Institute of Clinical Medicine, National Yang-Ming University; Division of Cardiology, Taipei Veterans General Hospital; 3 Institute of Biomedical Science, Academia Sinica; 4 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Objectives: Expression of adhesion molecules by endothelial cells and the attachment of leukocytes to the endothelium are critical early events in the development of atherosclerosis. Possible effects of antioxidants, including Cu/Zn superoxide dismutase (SOD), on adhesion molecule expression could play a key role in the prevention or treatment of cardiovascular disorders. Methods: Infection of human aortic endothelial cells (HAECs) with adenovirus carrying the human SOD gene (Ad-SOD) to investigate whether SOD overexpression in endothelial cells attenuate ROS production and adhesion molecules under tumor necrosis factor-α (TNF-α) stimulation by Western blot and cell-ELISA. To further examine potential interaction between the signaling cascades, we have focused on the effects of SOD overexpression to TNF-α-induced adhesion molecule expression through an examination of the relative influences of mitogen activator protein kinase (MAPKs) by Western blot. Results: Adenovirus-mediated gene transfer of human SOD gene resulted in a high level of SOD overexpression in HAECs by immunocytochemical staining, Western blot, and enzyme activity. SOD overexpression significantly suppressed the TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). SOD overexpression also reduced the binding of the human monocytic cell line, U937, to TNF-α-stimulated HAECs. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen activator protein kinase demonstrated that SOD overexpression suppressed ERK and p38 phosphorylation. SOD overexpression attenuated superoxide and hydrogen peroxide generation in both control and TNF-α-treated HAECs. Conclusions: These results suggest that SOD has anti-inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response. 2P-0466
Role of soluble adhesion molecules in the pathogenesis of hypertensive vascular lesions in obesity
M. Yamakado. Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Japan Objective: Monocyte adhesion on vascular endothelium by adhesion molecules is the first step for not only atherosclerosis but also hypertensive vascular lesions. However, clinical role of adhesion moleculaes in the pathogenesis of hypertensive vascular lesions is not yet clear, especially in obesity induced hypertension. To assess the role of adhesion molecules in that mechanism, the relationship between carotid-intima media thickness (IMT) as hypertensive vascular lesions and plasma levels of soluble adhesion molecules such as E-selectin, VCAM-1, and ICAM-1 was statistically analyzed. Methods: Four hundred and sixty one subjects who underwent annual health chech-ups at our center were enrolled in this study. Carotid IMT was measured by B-mode ultrasonography and plasma levels of adhesion molecules were by ELISA method. Results: VCAM-1 was significantly correlated with blood pressure (BP) (p<0.05), and body mass index (BMI) (p<0.01). There were no correlations between ICAM-1 and BP nor BMI. E-selectin and VCAM-1 were significantly correlated with BP (p<0.001), and BMI (p<0.001). Carotid IMT was significantly correlated with E-selectin (p<0.001). E-selectin and VCAM-1 were significantly increased with BP, and E-selectin was also singnificantly increased with BMI. There was no cross reaction between BP and BMI. Conclusion: E-selectin and VCAM-1 may play an important role in the pathogenesis of hypertensive vascular lesions, and E-selectin may be a key factor for obesity induce hypertensive vascular lesions.
2P-0467 ∗
Enhanced anti-inflammatory property of high density lipoprotein following infusion of chylomicron-like emulsions
S. Nicholls, K.-A. Rye, P. Barter. Heart Research Institute, Camperdown, NSW, Australia Introduction: High density lipoprotein (HDL) inhibits the cytokine induced expression of vascular cell adhesion molecule-1 (VCAM-1) by human endothelial vein endothelial cells (HUVECs). This depends on the phosphatidylcholine (PC) component of the HDL. We investigated the effect of phospholipid specific chylomicron-like emulsions on the (i) PC composition and (ii) anti-inflammatory activity of rabbit HDL. Method: Rabbits received an infusion of saline (group 1, n=5) or emulsions containing palmityl-linoleoyl PC (group 2, n=6) or palmityl-oleoyl PC (group 3, n=6). HDL was isolated from plasma collected after 20 minutes. Mass spectroscopy determined HDL PC composition. The ability of HDL to inhibit TNF stimulated expression of VCAM-1 was assessed by flow cytometry. Results: A proportion of the infused phospholipids were incorporated into the HDL fraction. This was associated with an enhanced ability of the HDL to inhibit the expression of VCAM-1 in HUVECs. At an apolipoprotein A-I (apoA-I) concentration of 4µM, the HDL from group 1-3 rabbits inhibited VCAM-1 expression in activated HUVECs by 21±5%, 56±13% and 53±12%, respectively (p< 0.05 for each comparison with group 1). When present at an apoA-I concentration of 8 µM the HDL from group 1-3 animals inhibited VCAM-1 expression by 46±7%, 79±9% and 79±9%, respectively (p< 0.02 for each comparison). The mechanism underlying this enhanced inhibitory activity of the HDL is uncertain. Conclusion: Infusion of chylomicron-like emulsions results in an incorporation of phospholipids into HDL. This is associated with an enhanced ability to inhibit the cytokine induced expression of VCAM-1. This highlights a potential enhanced anti-inflammatory role of HDL during the early postprandial phase. 2P-0468
Role of various adhesion and activation molecules in patients with established coronary artery disease
G. Dwivedi, A. Grover, Y.P. Sharma, R. Vijayvergia, A. Bhatnagar, S. Majumda. Post Graduate Institution of Medical Education and Research, India Objective: The objective of the study was to determine the role of various adhesion and activation molecules by estimating their levels in the peripheral and coronary sinus blood samples in patients with angiograhically proven CAD and to compare it with that of controls with normal coronary arteries. Methods: Various molecules like CD25(interleukin-2 receptor), CD54 (intercellular adhesion molecule-1), CD69 (early activation marker), CD3 (T-cell surface receptor), CD19 (B-cell surface receptor, and CD11 (receptor for ICAM) were estimated in the peripheral and coronary sinus blood samples in 20 cases and compared with 20 controls by FACScan (flow cytometer) by cell Quest Software (BD). Both the groups were matched for demographic and conventional CAD risk factors. Results: The results showed elevated values of CD25, CD54, CD69, CD3 and CD11b both in the coronary sinus and peripheral blood samples in cases as compared with controls (p<0.05). No significant difference was noted for CD19, CD11a and CD11c (p>0.1). Only CD54, CD69, CD11b and CD11c were elevated in the coronary sinus compared to peripheral blood samples in cases (p<0.05), while in controls CD69, CD25, CD54, CD11a and CD11b were elevated in the coronary sinus compared to peripheral blood samples (p<0.05). Conclusion: Adhesion and activation molecules like CD25, CD54, CD69, CD3 and CD11b were elevated in CAD patients. There is not much incremental benefit of estimating various molecules in the coronary sinus compared to peripheral blood samples. 2P-0469
Angiotensin II type I receptor antagonist, irbesartan, prevents vascular cell adhesion molecule-1 expression in a rabbit model of early atherosclerosis
Y. Sun 1 , D. Hu 1 , Y. Huang 2 . 1 Cardiology Department of Renmin Hospital, Peking University, Beijing; 2 Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, China Objective: To evaluate the effect of angiotensin II type I receptor antagonist Irbesartan on the expression of vascular cell adhesion molecule-1(VCAM-1)in a rabbit model of high-cholesterol diet induced atherosclerosis. XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
Tuesday September 30, 2003: Poster Session Adhesion molecules Adenovirus-mediated overexpression of superoxide dismutase attenuates VCAM-1 and ICAM-1 expression in TNF-α-treated human aortic endothelial cells
Y.L. Chen 1 , S.J. Lin 2 , Y.Y. Hung 1 , S.K. Shyue 3 , Y.H. Chen 4 , J.W. Chen 2 . 1 Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University; 2 Institute of Clinical Medicine, National Yang-Ming University; Division of Cardiology, Taipei Veterans General Hospital; 3 Institute of Biomedical Science, Academia Sinica; 4 Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Objectives: Expression of adhesion molecules by endothelial cells and the attachment of leukocytes to the endothelium are critical early events in the development of atherosclerosis. Possible effects of antioxidants, including Cu/Zn superoxide dismutase (SOD), on adhesion molecule expression could play a key role in the prevention or treatment of cardiovascular disorders. Methods: Infection of human aortic endothelial cells (HAECs) with adenovirus carrying the human SOD gene (Ad-SOD) to investigate whether SOD overexpression in endothelial cells attenuate ROS production and adhesion molecules under tumor necrosis factor-α (TNF-α) stimulation by Western blot and cell-ELISA. To further examine potential interaction between the signaling cascades, we have focused on the effects of SOD overexpression to TNF-α-induced adhesion molecule expression through an examination of the relative influences of mitogen activator protein kinase (MAPKs) by Western blot. Results: Adenovirus-mediated gene transfer of human SOD gene resulted in a high level of SOD overexpression in HAECs by immunocytochemical staining, Western blot, and enzyme activity. SOD overexpression significantly suppressed the TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1). SOD overexpression also reduced the binding of the human monocytic cell line, U937, to TNF-α-stimulated HAECs. Phosphorylation studies of ERK1/2, JNK, and p38, three subgroups of mitogen activator protein kinase demonstrated that SOD overexpression suppressed ERK and p38 phosphorylation. SOD overexpression attenuated superoxide and hydrogen peroxide generation in both control and TNF-α-treated HAECs. Conclusions: These results suggest that SOD has anti-inflammatory properties and may play important roles in the prevention of atherosclerosis and inflammatory response. 2P-0466
Role of soluble adhesion molecules in the pathogenesis of hypertensive vascular lesions in obesity
M. Yamakado. Center for Multiphasic Health Testing and Services, Mitsui Memorial Hospital, Japan Objective: Monocyte adhesion on vascular endothelium by adhesion molecules is the first step for not only atherosclerosis but also hypertensive vascular lesions. However, clinical role of adhesion moleculaes in the pathogenesis of hypertensive vascular lesions is not yet clear, especially in obesity induced hypertension. To assess the role of adhesion molecules in that mechanism, the relationship between carotid-intima media thickness (IMT) as hypertensive vascular lesions and plasma levels of soluble adhesion molecules such as E-selectin, VCAM-1, and ICAM-1 was statistically analyzed. Methods: Four hundred and sixty one subjects who underwent annual health chech-ups at our center were enrolled in this study. Carotid IMT was measured by B-mode ultrasonography and plasma levels of adhesion molecules were by ELISA method. Results: VCAM-1 was significantly correlated with blood pressure (BP) (p<0.05), and body mass index (BMI) (p<0.01). There were no correlations between ICAM-1 and BP nor BMI. E-selectin and VCAM-1 were significantly correlated with BP (p<0.001), and BMI (p<0.001). Carotid IMT was significantly correlated with E-selectin (p<0.001). E-selectin and VCAM-1 were significantly increased with BP, and E-selectin was also singnificantly increased with BMI. There was no cross reaction between BP and BMI. Conclusion: E-selectin and VCAM-1 may play an important role in the pathogenesis of hypertensive vascular lesions, and E-selectin may be a key factor for obesity induce hypertensive vascular lesions.
2P-0467 ∗
Enhanced anti-inflammatory property of high density lipoprotein following infusion of chylomicron-like emulsions
S. Nicholls, K.-A. Rye, P. Barter. Heart Research Institute, Camperdown, NSW, Australia Introduction: High density lipoprotein (HDL) inhibits the cytokine induced expression of vascular cell adhesion molecule-1 (VCAM-1) by human endothelial vein endothelial cells (HUVECs). This depends on the phosphatidylcholine (PC) component of the HDL. We investigated the effect of phospholipid specific chylomicron-like emulsions on the (i) PC composition and (ii) anti-inflammatory activity of rabbit HDL. Method: Rabbits received an infusion of saline (group 1, n=5) or emulsions containing palmityl-linoleoyl PC (group 2, n=6) or palmityl-oleoyl PC (group 3, n=6). HDL was isolated from plasma collected after 20 minutes. Mass spectroscopy determined HDL PC composition. The ability of HDL to inhibit TNF stimulated expression of VCAM-1 was assessed by flow cytometry. Results: A proportion of the infused phospholipids were incorporated into the HDL fraction. This was associated with an enhanced ability of the HDL to inhibit the expression of VCAM-1 in HUVECs. At an apolipoprotein A-I (apoA-I) concentration of 4µM, the HDL from group 1-3 rabbits inhibited VCAM-1 expression in activated HUVECs by 21±5%, 56±13% and 53±12%, respectively (p< 0.05 for each comparison with group 1). When present at an apoA-I concentration of 8 µM the HDL from group 1-3 animals inhibited VCAM-1 expression by 46±7%, 79±9% and 79±9%, respectively (p< 0.02 for each comparison). The mechanism underlying this enhanced inhibitory activity of the HDL is uncertain. Conclusion: Infusion of chylomicron-like emulsions results in an incorporation of phospholipids into HDL. This is associated with an enhanced ability to inhibit the cytokine induced expression of VCAM-1. This highlights a potential enhanced anti-inflammatory role of HDL during the early postprandial phase. 2P-0468
Role of various adhesion and activation molecules in patients with established coronary artery disease
G. Dwivedi, A. Grover, Y.P. Sharma, R. Vijayvergia, A. Bhatnagar, S. Majumda. Post Graduate Institution of Medical Education and Research, India Objective: The objective of the study was to determine the role of various adhesion and activation molecules by estimating their levels in the peripheral and coronary sinus blood samples in patients with angiograhically proven CAD and to compare it with that of controls with normal coronary arteries. Methods: Various molecules like CD25(interleukin-2 receptor), CD54 (intercellular adhesion molecule-1), CD69 (early activation marker), CD3 (T-cell surface receptor), CD19 (B-cell surface receptor, and CD11 (receptor for ICAM) were estimated in the peripheral and coronary sinus blood samples in 20 cases and compared with 20 controls by FACScan (flow cytometer) by cell Quest Software (BD). Both the groups were matched for demographic and conventional CAD risk factors. Results: The results showed elevated values of CD25, CD54, CD69, CD3 and CD11b both in the coronary sinus and peripheral blood samples in cases as compared with controls (p<0.05). No significant difference was noted for CD19, CD11a and CD11c (p>0.1). Only CD54, CD69, CD11b and CD11c were elevated in the coronary sinus compared to peripheral blood samples in cases (p<0.05), while in controls CD69, CD25, CD54, CD11a and CD11b were elevated in the coronary sinus compared to peripheral blood samples (p<0.05). Conclusion: Adhesion and activation molecules like CD25, CD54, CD69, CD3 and CD11b were elevated in CAD patients. There is not much incremental benefit of estimating various molecules in the coronary sinus compared to peripheral blood samples. 2P-0469
Angiotensin II type I receptor antagonist, irbesartan, prevents vascular cell adhesion molecule-1 expression in a rabbit model of early atherosclerosis
Y. Sun 1 , D. Hu 1 , Y. Huang 2 . 1 Cardiology Department of Renmin Hospital, Peking University, Beijing; 2 Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, China Objective: To evaluate the effect of angiotensin II type I receptor antagonist Irbesartan on the expression of vascular cell adhesion molecule-1(VCAM-1)in a rabbit model of high-cholesterol diet induced atherosclerosis. XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan