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NEOPTERIN PLASMA WAS ASSOCIATED WITH INCREASED RISK OF CARDIOVASCULAR EVENTS IN ACUTE CORONARY SYNDROMES IN BALI ISLAND
Poster Sessions PO19 Vascular endothelium
64 PO18-190
TOF-SIMS A TOOL FOR DETECTING ALTERATIONS OF LIPIDS IN THE RAT AORTIC WALL AS AN EFFECT OF HIGH GLUCOSE INTAKE
Y.M. Magnusson, P.F. Friberg, Y.C. Chen. Institution of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden Aim: To use TOF-SIMS (Time of Flight – Secondary Ion Mass Spectrometry) to analyse the lipid composition as an effect of high glucose intake in the rat aortic wall. Introduction: Intake of high carbohydrate diets is known to results in alteration in the plasma lipids with elevated plasma triglycerides and alteration in the fatty acid metabolism. Studies have shown that sucrose induces changes in the fatty acid composition in phospholipids of the membranes of the aortic wall. TOF-SIMS is a new method to identify lipids of the surface of biological tissues. Method: The animals were divided into two groups, drinking water with or without 10% glucose from birth to 6 months of age. The aortic wall was high pressure frozen, freeze fractured, freeze dried and analysed by TOF-SIMS. Surface spectra were taken from standardized regions of the vessel wall. Peaks were selected and compared between groups. A conventional t-test was used to statistically compare significant difference between the groups. Results: Significant difference was detected in the lipid composition in the glucose drinking rats as compared with that from control rats as followed: a decrease of the ratio of polyunsaturated fatty acids compared to monounsaturated fatty acids were found in the high glucose intake group in diacylglycerol, triacylglycerol and between peaks of fatty acids. Moreover, a decreased ratio of cholesterol to phosphocholine in the glucose drinking rats was detected. Conclusions: TOF-SIMS can be used to evaluate the effect of highglucose intake of the lipid alteration in the rat aortic wall.
PO19 VASCULAR ENDOTHELIUM PO19-191
GENISTEIN, AN ISOFLAVONE INHIBITS RAT AORTIC SMOOTH MUSCLE CELL PROLIFERATION AND CELL CYCLE THROUGH THE REGULATION OF CELL CYCLE-RELATED PROTEINS
J. Yu 1 , T. Kim 1 , J. Lee 1 , M. Tudev 1 , H. Shin 2 , Y. Yun 1 . 1 College of Pharmacy, CBITRC, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea; 2 College of Natural Sciences, Konkuk University, Chungju, Korea Diet can be the most important factor that influences risks for cardiovascular diseases. Genistein, an isoflavone included in soy, is one candidate that may benefit the cardiovascular system. Here, we have investigated the effect of genistein on the platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Genistein significantly inhibited 25 ng/mL PDGF-BB-induced rat aortic VSMCs proliferation and [3H]-thymidine incorporation into DNA at 10, 20, and 40 µM. In accordance with these findings, genistein revealed blocking of the PDGF-BB-induced progression through G0/G1 to S phase of the cell cycle in synchronized cells. Western blot showed that genistein inhibited phosphorylation of retinoblastoma protein (pRb) and expression of cyclin E and cyclin-dependent kinase 2 (CDK2), while did not affect early signaling transduction such as PDGF beta-receptor, extracellular signal-regulated kinase (ERK) 1/2, Akt and PLCγ1 phosphorylation. Taken together, these results suggest that genistein inhibits PDGF-BB-induced rat aortic VSMCs proliferation via G0/G1 arrest in association with modulation of the expression or activation of cell-cycle regulatory proteins, which may contribute to the beneficial effect of genistein on cardiovascular system. PO19-192
NEOPTERIN PLASMA WAS ASSOCIATED WITH INCREASED RISK OF CARDIOVASCULAR EVENTS IN ACUTE CORONARY SYNDROMES IN BALI ISLAND
W.S. Wardani 3 , A. Santoso 1 , K. Suryana 2 . 1 Department of Cardiology-Vascular Medicine, 2 Department of Internal Medicine, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia; 3 Department of Internal Medicine, Sanglah Hospital, Denpasar, Bali, Indonesia Background and aims: Neopterin is a biomarker of monocyte activation
and it might be expressed in atherosclerosis. There has been lacking of information on the prognostic role of neopterin in acute coronary syndromes (ACS). The study was to measure the associations of high neopterin level and increased risk of cardiovascular events in ACS in Bali Island. Methods: This was a prospective cohort study, recruited 71 patients with ACS from January 31, 2007 through August 31, 2007 in Sanglah Hospital of Udayana School of Medicine, Bali. Cardiovascular (CV) events such as: CV death, acute myocardial infarction, stroke and recurrent myocardial ischemia were previously determined. Relative risk was measured using Cox proportional model, and survival rate was determined by Kaplan-Meier curve. Results: Of 71 ACS patients aged 56.8±9.5 years, 21 (29.5%) subjects underwent CV events. Median follow-up was 151.6 (95% CI: 129.7 – 173.5) days. Baseline characteristics were similarly distributed between groups with highest quartile neopterin level (≥ 14.7 nmol/L) than those with lowest quartile group (≤ 6.2 nmol/L). Group with the highest quartile had the worst survival curve than those with the lowest quartile group (log-rank test; P = 0.04). On Cox proportional model, relative risk of highest quartile of neopterin was 5.8 (95% CI: 1.2 – 28.4; P = 0.02) compared to lowest quartile, after adjustment of other predictors. Conclusions: High level of neopterin plasma was associated with increased risk of CV events among those with ACS in Bali Island. PO19-193
OBOVATOL INHIBITS INTIMAL HYPERPLASIA AFTER CAROTID ARTERY INJURY BY INDUCTION OF P21 PROTEIN
Y. Lim 1 , T. Kim 1 , J. Kwon 2 , D. Kim 2 , S. Lee 3 , B. Kwon 4 , J. Hong 1 , Y. Yun 1 . 1 College of Pharmacy, CBITRC, Chungbuk National University, Cheongju, Korea; 2 College of Medicine, Chungbuk National University, Cheongju, Korea; 3 KT&G Central Research Institute, Daejeon, Korea; 4 Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cells (VSMCs) proliferation and migration. Obovatol, an active component extracted from Magnolila obovata leaves, has various pharmacological effects, including potent antioxidant activity. In the present study, we investigated the ability of obovatol to inhibit on the migration and proliferation in cultured VSMCs and neointima formation after carotid artery injury in rats. Obovatol (1 to 5 µM) produced a concentration-dependent inhibition of 5% FBS or platelet-derived growth factor (PDGF)-BB-elicited VSMC migration and proliferation, respectively. There was no evidence of cellular toxicity or apoptosis as determined by trypan blue exclusion and Annexin-V binding analyses. Additionally, treatment with obovatol blocks the cell cycle in the G1 phase, down-regulates the expression of cyclins and CDKs and up-regulates the expression of p21Cip1 (p21), a CDK inhibitor. Next, rat balloon-injured carotid artery was analyzed for intimal thickening and p21 expression. The angiographic minimum luminal diameters of the obovatol groups treated at 100 µg and 1 mg were 0.78±0.06 and 0.77±0.07 AU, and these were significantly larger than that of the control group (0.58±0.07 AU). The obovatol groups (100 µg, 1 mg; 0.14±0.04, 0.09±0.03 mm2 ) showed significant neointimal formation reductions versus the control group (0.17±0.02 mm2 ). Immunohistochemical staining demonstrated that, in obovatol-treated rats, p21 was strongly expressed in the neointima. Taken together, these data suggest that obovatol may inhibit VSMCs proliferation by perturbing cell cycle progression, which may be due to the activation of p21 pathway. PO19-194
THE ANTIPROLIFERATIVE MECHANISM OF CUDRAFLAVONE B ON RAT AROTIC SMOOTH MUSCLE CELLS
T. Kim, H. Han, J. Im, B. Hwang, Y. Yun. College of Pharmacy, CBITRC, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea Cudrania tricuspidata has been proposed to play a role in anti-inflammatory, antioxidant, hepatoprotective and anti-tumor activity. Although cudraflavone B has a variety of pharmacological effects, its effects on vascular smooth muscle cells (VSMCs) are unclear. In the present study, cudraflavone B was found to inhibit cell proliferation and DNA synthesis in cultured VSMCs. Cudraflavone B inhibited [3H]-thymidine incorporations into DNA in VSMCs that occurred in response to treatment with 25 ng/ml PDGF-BB. PDGF-BB-stimulated DNA synthesis was significantly reduced
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey
64 PO18-190
TOF-SIMS A TOOL FOR DETECTING ALTERATIONS OF LIPIDS IN THE RAT AORTIC WALL AS AN EFFECT OF HIGH GLUCOSE INTAKE
Y.M. Magnusson, P.F. Friberg, Y.C. Chen. Institution of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden Aim: To use TOF-SIMS (Time of Flight – Secondary Ion Mass Spectrometry) to analyse the lipid composition as an effect of high glucose intake in the rat aortic wall. Introduction: Intake of high carbohydrate diets is known to results in alteration in the plasma lipids with elevated plasma triglycerides and alteration in the fatty acid metabolism. Studies have shown that sucrose induces changes in the fatty acid composition in phospholipids of the membranes of the aortic wall. TOF-SIMS is a new method to identify lipids of the surface of biological tissues. Method: The animals were divided into two groups, drinking water with or without 10% glucose from birth to 6 months of age. The aortic wall was high pressure frozen, freeze fractured, freeze dried and analysed by TOF-SIMS. Surface spectra were taken from standardized regions of the vessel wall. Peaks were selected and compared between groups. A conventional t-test was used to statistically compare significant difference between the groups. Results: Significant difference was detected in the lipid composition in the glucose drinking rats as compared with that from control rats as followed: a decrease of the ratio of polyunsaturated fatty acids compared to monounsaturated fatty acids were found in the high glucose intake group in diacylglycerol, triacylglycerol and between peaks of fatty acids. Moreover, a decreased ratio of cholesterol to phosphocholine in the glucose drinking rats was detected. Conclusions: TOF-SIMS can be used to evaluate the effect of highglucose intake of the lipid alteration in the rat aortic wall.
PO19 VASCULAR ENDOTHELIUM PO19-191
GENISTEIN, AN ISOFLAVONE INHIBITS RAT AORTIC SMOOTH MUSCLE CELL PROLIFERATION AND CELL CYCLE THROUGH THE REGULATION OF CELL CYCLE-RELATED PROTEINS
J. Yu 1 , T. Kim 1 , J. Lee 1 , M. Tudev 1 , H. Shin 2 , Y. Yun 1 . 1 College of Pharmacy, CBITRC, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea; 2 College of Natural Sciences, Konkuk University, Chungju, Korea Diet can be the most important factor that influences risks for cardiovascular diseases. Genistein, an isoflavone included in soy, is one candidate that may benefit the cardiovascular system. Here, we have investigated the effect of genistein on the platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Genistein significantly inhibited 25 ng/mL PDGF-BB-induced rat aortic VSMCs proliferation and [3H]-thymidine incorporation into DNA at 10, 20, and 40 µM. In accordance with these findings, genistein revealed blocking of the PDGF-BB-induced progression through G0/G1 to S phase of the cell cycle in synchronized cells. Western blot showed that genistein inhibited phosphorylation of retinoblastoma protein (pRb) and expression of cyclin E and cyclin-dependent kinase 2 (CDK2), while did not affect early signaling transduction such as PDGF beta-receptor, extracellular signal-regulated kinase (ERK) 1/2, Akt and PLCγ1 phosphorylation. Taken together, these results suggest that genistein inhibits PDGF-BB-induced rat aortic VSMCs proliferation via G0/G1 arrest in association with modulation of the expression or activation of cell-cycle regulatory proteins, which may contribute to the beneficial effect of genistein on cardiovascular system. PO19-192
NEOPTERIN PLASMA WAS ASSOCIATED WITH INCREASED RISK OF CARDIOVASCULAR EVENTS IN ACUTE CORONARY SYNDROMES IN BALI ISLAND
W.S. Wardani 3 , A. Santoso 1 , K. Suryana 2 . 1 Department of Cardiology-Vascular Medicine, 2 Department of Internal Medicine, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia; 3 Department of Internal Medicine, Sanglah Hospital, Denpasar, Bali, Indonesia Background and aims: Neopterin is a biomarker of monocyte activation
and it might be expressed in atherosclerosis. There has been lacking of information on the prognostic role of neopterin in acute coronary syndromes (ACS). The study was to measure the associations of high neopterin level and increased risk of cardiovascular events in ACS in Bali Island. Methods: This was a prospective cohort study, recruited 71 patients with ACS from January 31, 2007 through August 31, 2007 in Sanglah Hospital of Udayana School of Medicine, Bali. Cardiovascular (CV) events such as: CV death, acute myocardial infarction, stroke and recurrent myocardial ischemia were previously determined. Relative risk was measured using Cox proportional model, and survival rate was determined by Kaplan-Meier curve. Results: Of 71 ACS patients aged 56.8±9.5 years, 21 (29.5%) subjects underwent CV events. Median follow-up was 151.6 (95% CI: 129.7 – 173.5) days. Baseline characteristics were similarly distributed between groups with highest quartile neopterin level (≥ 14.7 nmol/L) than those with lowest quartile group (≤ 6.2 nmol/L). Group with the highest quartile had the worst survival curve than those with the lowest quartile group (log-rank test; P = 0.04). On Cox proportional model, relative risk of highest quartile of neopterin was 5.8 (95% CI: 1.2 – 28.4; P = 0.02) compared to lowest quartile, after adjustment of other predictors. Conclusions: High level of neopterin plasma was associated with increased risk of CV events among those with ACS in Bali Island. PO19-193
OBOVATOL INHIBITS INTIMAL HYPERPLASIA AFTER CAROTID ARTERY INJURY BY INDUCTION OF P21 PROTEIN
Y. Lim 1 , T. Kim 1 , J. Kwon 2 , D. Kim 2 , S. Lee 3 , B. Kwon 4 , J. Hong 1 , Y. Yun 1 . 1 College of Pharmacy, CBITRC, Chungbuk National University, Cheongju, Korea; 2 College of Medicine, Chungbuk National University, Cheongju, Korea; 3 KT&G Central Research Institute, Daejeon, Korea; 4 Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea Restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs due to vascular smooth muscle cells (VSMCs) proliferation and migration. Obovatol, an active component extracted from Magnolila obovata leaves, has various pharmacological effects, including potent antioxidant activity. In the present study, we investigated the ability of obovatol to inhibit on the migration and proliferation in cultured VSMCs and neointima formation after carotid artery injury in rats. Obovatol (1 to 5 µM) produced a concentration-dependent inhibition of 5% FBS or platelet-derived growth factor (PDGF)-BB-elicited VSMC migration and proliferation, respectively. There was no evidence of cellular toxicity or apoptosis as determined by trypan blue exclusion and Annexin-V binding analyses. Additionally, treatment with obovatol blocks the cell cycle in the G1 phase, down-regulates the expression of cyclins and CDKs and up-regulates the expression of p21Cip1 (p21), a CDK inhibitor. Next, rat balloon-injured carotid artery was analyzed for intimal thickening and p21 expression. The angiographic minimum luminal diameters of the obovatol groups treated at 100 µg and 1 mg were 0.78±0.06 and 0.77±0.07 AU, and these were significantly larger than that of the control group (0.58±0.07 AU). The obovatol groups (100 µg, 1 mg; 0.14±0.04, 0.09±0.03 mm2 ) showed significant neointimal formation reductions versus the control group (0.17±0.02 mm2 ). Immunohistochemical staining demonstrated that, in obovatol-treated rats, p21 was strongly expressed in the neointima. Taken together, these data suggest that obovatol may inhibit VSMCs proliferation by perturbing cell cycle progression, which may be due to the activation of p21 pathway. PO19-194
THE ANTIPROLIFERATIVE MECHANISM OF CUDRAFLAVONE B ON RAT AROTIC SMOOTH MUSCLE CELLS
T. Kim, H. Han, J. Im, B. Hwang, Y. Yun. College of Pharmacy, CBITRC, Research Center for Bioresource and Health, Chungbuk National University, Cheongju, Korea Cudrania tricuspidata has been proposed to play a role in anti-inflammatory, antioxidant, hepatoprotective and anti-tumor activity. Although cudraflavone B has a variety of pharmacological effects, its effects on vascular smooth muscle cells (VSMCs) are unclear. In the present study, cudraflavone B was found to inhibit cell proliferation and DNA synthesis in cultured VSMCs. Cudraflavone B inhibited [3H]-thymidine incorporations into DNA in VSMCs that occurred in response to treatment with 25 ng/ml PDGF-BB. PDGF-BB-stimulated DNA synthesis was significantly reduced
77th Congress of the European Atherosclerosis Society, April 26–29, 2008, Istanbul, Turkey