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Regulated expression of endothelial lipase in atherosclerosis
Abstracts
cholesterol-lowering effect as well as potential pleiotropic effects. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. It has been demonstrated that statins could inhibit secretion of metalloproteinases from vascular smooth muscle cells and macrophages in vitro. This study investigated the effects of rosuvastatin on sterol synthesis and the expression of matrix metalloproteinases in LDLR-deficient mice. Methods: LDLR-deficient mice on a high-fat and high-cholesterol diet developed plasma hyperlipemia and atherosclerosis. They were randomly given into rosuvastatin group (n = 8), control group (n = 8), and they were sacrificed after 12 weeks. We examined the levels of plasma lipid; the expression of MMP-2 and MMP-9 with zymography; the morphological of the aorta artery; the H&E and immunohistochemical with aorta sinus. Conclusions: Rosuvastatin inhibits MMP-2 and MMP-9 expression and improves the progression of atherosclerosis in LDLR-deficient mice exposed to a high-fat and high-cholesterol diet. This may be one of the pleiotropic effects of rosuvastatin and benefits the therapy of many kinds of dyslipidemia, including familial hypercholesterolemia. doi:10.1016/j.ijcard.2009.09.007 AT000282 Chinese yellow wine improved atherosclerotic plaque by lowering matrix metalloproteinase-2 in LDL receptor knockout mice
S3
model was established by in vivo administering vitamin D2 (VD) combined with high cholesterol diet (HCD). Rats in control group were fed with standard chow without administering VD. After 12 weeks, blood was collected to test serum lipid and the rats are sacrificed. Arteries were isolated, some of which were subjected to HE staining or immunochemistry staining and the others were kept for real time PCR and Western blotting. In vitro we treated Raw264.7 cells with LPS to examine the expression of EL and NFκB by real time PCR and Western blotting. We also explored the effects of PDTC, a NFκB inhibitor on LPS induced EL expression. EMSA was performed to investigate whether LPS stimulate NFκB binding to EL promoter. Results: We established HCD induced atherosclerosis model in rats and observed serum lipid disorder and atheromatous plaque. Western blotting and immunochemistry staining revealed that EL expression was increased in the aorta, especially the atherosclerotic lesions of HCD rats compared with control rats. Treatment of Raw264.7 cells with LPS increased EL expression in a time and dose dependent manner. 100 ng/ml LPS induces EL expression to a peak level, 2.91 ± 0.63 fold (P < 0.01, n = 4) at 24 h. 100 ng/ml LPS stimulated IκBα degradation and nuclear NFκB phosphorylation at 30 min. NFκB inhibitor, PDTC, ameliorated the effects of LPS on EL. LPS stimulated NFκB binding to EL promoter. Conclusion: EL was upregulated in the artery of rat atherosclerosis. LPS stimulates EL expression in vitro through NFκB activation. doi:10.1016/j.ijcard.2009.09.009
JUFANG CHI, HANGYUAN GUO Department of Cardiology, Shaoxing People's Hospital, the First Affiliated Hospital of Shaoxing University, China
AT000327 Drug-eluting stent implantation versus coronary artery bypass grafting in smoking patients with three-vessel coronary disease
Objectives: To moderate consumption of wine is associated with the reduction of atherosclerotic lesion progression, and can reduce morbidity and mortality from cardiovascular disease. Our previous study found that Chinese yellow wine can inhibit the production of homocysteine-induced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells, the present research aimed to study whether Chinese yellow wine can inhibit MMP-2 and improve atherosclerosis in LDL receptor knockout mice vivo. Methods: Twenty four LDL receptor knockout mice on a high-fat and l-methionine diet developed plasma hyperhomocysteine and atherosclerosis, and they were randomly divided into yellow wine group (n = 8), red wine group (n = 8) and control group (n = 8), and they were sacrificed after 14 weeks. We examined the levels of plasma lipid and homocysteine, the production of MMP-2, the morphology of the aorta artery, and the H&E and immunohistochemical staining of aorta sinus. Conclusions: Chinese yellow wine can inhibit MMP-2 and improve atherosclerosis, and maybe both red wine and yellow wine have beneficial effects on cardiovascular disease by lowering MMP-2.
DI WU The First Affiliated Hospital of China Medical University, China
doi:10.1016/j.ijcard.2009.09.008 AT000309 Regulated expression of endothelial lipase in atherosclerosis XIAOQIAN WU, JIANGDONG LUO, PEIQING LIU School of Pharmaceutical Sciences, Sun Yat-sen University, China Objectives: Endothelial lipase (EL) is a major determinant of HDL metabolism, suggesting that it may be involved in the development of atherosclerosis. To understand the expression and regulation of EL in atherosclerosis, our study established high cholesterol diet (HCD)induced atherosclerosis model in rats. Further we explored the potential mechanisms regulating endothelial lipase expression by employing LPS on Raw264.7 cells in vitro. Methods: Atherosclerosis rat
Objective: To compare the twelve-month effectiveness of percutaneous coronary intervention with drug-eluting stent (DES-PCI) and coronary artery bypass grafting (CABG) in smokicxxng patients with three-vessel coronary disease. Methods: 91 smoking patients with three-vessel disease who received elective revascularization between July 2006 and November 2007 were included and divided into two groups: PCI group (n = 54) and CABG group (n = 37).We compared: ① the difference in twelve-month occurrence of Major Adverse Cardiac and Cerebrovascular Event (MACCE) and reoccurrence of angina pectoris (AP) between PCI group and CABG group, ② the difference in twelve-month occurrence of MACCE and reoccurrence of AP between PCI group and CABG group in patients with left main coronary disease, long diffuse coronary disease, chronic occlusion and bifurcate coronary disease, and ③ the difference in twelve-month occurrence of MACCE and reoccurrence of AP between patients who underwent complete revascularization (CR) and incomplete revascularization (IR). Results: ① At 1 year, there was no statistical difference between PCI group and CABG group in the occurrence of MACCE (14.8%:24.3%, P = 0.253, OR = 0.541, 95%CI 0.187–1.565) and reoccurrence of AP (24.1%:29.7%, P = 0.547, OR = 0.749, 95%CI 0.292– 1.921). ② The difference of MACCE occurrence within 12 months was not statistically significant between PCI group and CABG group in patients with left main coronary disease (18.2%:35.7%, P = 0.305, OR = 0.400, 95%CI 0.061–2.627), long diffuse disease (31.3%:22.2%, P = 0.551, OR = 1.591, 95%CI 0.343–7.374), chronic occlusion (20.0%:12.5%, P = 0.570, OR = 1.750, 95%CI 0.249–12.279) and bifurcate coronary disease (20.0%:37.5%, P = 0.490, OR = 0.417, 95%CI 0.030–5.708). There was no statistical difference of AP reoccurrence between PCI group and CABG group in the above subgroups. ③ The difference of MACCE occurrence within 12 months between CR patients and IR patients was not statistically significant (29.8%:22.7%, P = 0.445, OR = 1.442, 95% CI 0.562–3.701), and it is
cholesterol-lowering effect as well as potential pleiotropic effects. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. It has been demonstrated that statins could inhibit secretion of metalloproteinases from vascular smooth muscle cells and macrophages in vitro. This study investigated the effects of rosuvastatin on sterol synthesis and the expression of matrix metalloproteinases in LDLR-deficient mice. Methods: LDLR-deficient mice on a high-fat and high-cholesterol diet developed plasma hyperlipemia and atherosclerosis. They were randomly given into rosuvastatin group (n = 8), control group (n = 8), and they were sacrificed after 12 weeks. We examined the levels of plasma lipid; the expression of MMP-2 and MMP-9 with zymography; the morphological of the aorta artery; the H&E and immunohistochemical with aorta sinus. Conclusions: Rosuvastatin inhibits MMP-2 and MMP-9 expression and improves the progression of atherosclerosis in LDLR-deficient mice exposed to a high-fat and high-cholesterol diet. This may be one of the pleiotropic effects of rosuvastatin and benefits the therapy of many kinds of dyslipidemia, including familial hypercholesterolemia. doi:10.1016/j.ijcard.2009.09.007 AT000282 Chinese yellow wine improved atherosclerotic plaque by lowering matrix metalloproteinase-2 in LDL receptor knockout mice
S3
model was established by in vivo administering vitamin D2 (VD) combined with high cholesterol diet (HCD). Rats in control group were fed with standard chow without administering VD. After 12 weeks, blood was collected to test serum lipid and the rats are sacrificed. Arteries were isolated, some of which were subjected to HE staining or immunochemistry staining and the others were kept for real time PCR and Western blotting. In vitro we treated Raw264.7 cells with LPS to examine the expression of EL and NFκB by real time PCR and Western blotting. We also explored the effects of PDTC, a NFκB inhibitor on LPS induced EL expression. EMSA was performed to investigate whether LPS stimulate NFκB binding to EL promoter. Results: We established HCD induced atherosclerosis model in rats and observed serum lipid disorder and atheromatous plaque. Western blotting and immunochemistry staining revealed that EL expression was increased in the aorta, especially the atherosclerotic lesions of HCD rats compared with control rats. Treatment of Raw264.7 cells with LPS increased EL expression in a time and dose dependent manner. 100 ng/ml LPS induces EL expression to a peak level, 2.91 ± 0.63 fold (P < 0.01, n = 4) at 24 h. 100 ng/ml LPS stimulated IκBα degradation and nuclear NFκB phosphorylation at 30 min. NFκB inhibitor, PDTC, ameliorated the effects of LPS on EL. LPS stimulated NFκB binding to EL promoter. Conclusion: EL was upregulated in the artery of rat atherosclerosis. LPS stimulates EL expression in vitro through NFκB activation. doi:10.1016/j.ijcard.2009.09.009
JUFANG CHI, HANGYUAN GUO Department of Cardiology, Shaoxing People's Hospital, the First Affiliated Hospital of Shaoxing University, China
AT000327 Drug-eluting stent implantation versus coronary artery bypass grafting in smoking patients with three-vessel coronary disease
Objectives: To moderate consumption of wine is associated with the reduction of atherosclerotic lesion progression, and can reduce morbidity and mortality from cardiovascular disease. Our previous study found that Chinese yellow wine can inhibit the production of homocysteine-induced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells, the present research aimed to study whether Chinese yellow wine can inhibit MMP-2 and improve atherosclerosis in LDL receptor knockout mice vivo. Methods: Twenty four LDL receptor knockout mice on a high-fat and l-methionine diet developed plasma hyperhomocysteine and atherosclerosis, and they were randomly divided into yellow wine group (n = 8), red wine group (n = 8) and control group (n = 8), and they were sacrificed after 14 weeks. We examined the levels of plasma lipid and homocysteine, the production of MMP-2, the morphology of the aorta artery, and the H&E and immunohistochemical staining of aorta sinus. Conclusions: Chinese yellow wine can inhibit MMP-2 and improve atherosclerosis, and maybe both red wine and yellow wine have beneficial effects on cardiovascular disease by lowering MMP-2.
DI WU The First Affiliated Hospital of China Medical University, China
doi:10.1016/j.ijcard.2009.09.008 AT000309 Regulated expression of endothelial lipase in atherosclerosis XIAOQIAN WU, JIANGDONG LUO, PEIQING LIU School of Pharmaceutical Sciences, Sun Yat-sen University, China Objectives: Endothelial lipase (EL) is a major determinant of HDL metabolism, suggesting that it may be involved in the development of atherosclerosis. To understand the expression and regulation of EL in atherosclerosis, our study established high cholesterol diet (HCD)induced atherosclerosis model in rats. Further we explored the potential mechanisms regulating endothelial lipase expression by employing LPS on Raw264.7 cells in vitro. Methods: Atherosclerosis rat
Objective: To compare the twelve-month effectiveness of percutaneous coronary intervention with drug-eluting stent (DES-PCI) and coronary artery bypass grafting (CABG) in smokicxxng patients with three-vessel coronary disease. Methods: 91 smoking patients with three-vessel disease who received elective revascularization between July 2006 and November 2007 were included and divided into two groups: PCI group (n = 54) and CABG group (n = 37).We compared: ① the difference in twelve-month occurrence of Major Adverse Cardiac and Cerebrovascular Event (MACCE) and reoccurrence of angina pectoris (AP) between PCI group and CABG group, ② the difference in twelve-month occurrence of MACCE and reoccurrence of AP between PCI group and CABG group in patients with left main coronary disease, long diffuse coronary disease, chronic occlusion and bifurcate coronary disease, and ③ the difference in twelve-month occurrence of MACCE and reoccurrence of AP between patients who underwent complete revascularization (CR) and incomplete revascularization (IR). Results: ① At 1 year, there was no statistical difference between PCI group and CABG group in the occurrence of MACCE (14.8%:24.3%, P = 0.253, OR = 0.541, 95%CI 0.187–1.565) and reoccurrence of AP (24.1%:29.7%, P = 0.547, OR = 0.749, 95%CI 0.292– 1.921). ② The difference of MACCE occurrence within 12 months was not statistically significant between PCI group and CABG group in patients with left main coronary disease (18.2%:35.7%, P = 0.305, OR = 0.400, 95%CI 0.061–2.627), long diffuse disease (31.3%:22.2%, P = 0.551, OR = 1.591, 95%CI 0.343–7.374), chronic occlusion (20.0%:12.5%, P = 0.570, OR = 1.750, 95%CI 0.249–12.279) and bifurcate coronary disease (20.0%:37.5%, P = 0.490, OR = 0.417, 95%CI 0.030–5.708). There was no statistical difference of AP reoccurrence between PCI group and CABG group in the above subgroups. ③ The difference of MACCE occurrence within 12 months between CR patients and IR patients was not statistically significant (29.8%:22.7%, P = 0.445, OR = 1.442, 95% CI 0.562–3.701), and it is