1.Lectin-like oxidized low-density lipoprotein receptor-1: protein, ligands, expression and pathophysiological significance.
Chinese Medical Journal 2007;120(5):421-426
OBJECTIVETo review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED (1997 - 2006) online resources using the key term LOX-1.
STUDY SELECTIONMainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.
RESULTSThe key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed.
CONCLUSIONSIdentification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.
Animals ; Arthritis, Rheumatoid ; etiology ; Atherosclerosis ; etiology ; Humans ; Ligands ; Myocardial Infarction ; etiology ; Osteoarthritis ; etiology ; Scavenger Receptors, Class E ; chemistry ; genetics ; physiology
2.Study on visfatin-induced inflammation and necroptosis via LOX-1 in human umbilical vein endothelial cells.
Xiaoyu HAN ; Wenchao WU ; Xiaojing LIU ; Ye ZHU
Journal of Biomedical Engineering 2020;37(5):834-841
The aim of the study is to identify the effects and underlying mechanisms of visfatin on inflammation and necroptosis in vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with visfatin or pretreated with Polyinosinic acid (LOX-1 inhibitor). By using the Western blot, RT-PCR, immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), MTT and flow cytometry technique, the occurrence of inflammation and necroptosis in HUVECs were evaluated. Our results showed that 100 ng/mL visfatin significantly increased the mRNA and protein expression of monocyte chemotactic protein 1 (MCP-1) and LOX-1 after 24 hours' treatment in HUVECs. However, pretreatment with Polyinosinic acid could significantly reduce the expression of MCP-1 compared with visfatin group. Additionally, 100 ng/mL visfatin could induce the production of necrotic features and increase the mRNA expression of BMF (one of the markers of necroptosis), while pretreating with Polyinosinic acid markedly downregulated the mRNA expression of BMF gene and promoted the cell proliferation. These results indicate that visfatin might induce inflammation and necroptosis via LOX-1 in HUVECs, suggesting that visfatin plays a central role in the development of atherosclerosis.
Cells, Cultured
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Human Umbilical Vein Endothelial Cells
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Humans
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Inflammation/chemically induced*
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Necroptosis
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Nicotinamide Phosphoribosyltransferase
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Scavenger Receptors, Class E/genetics*
3.Effects of miR-590-5p on ox-LDL-induced endothelial cells apoptosis and LOX-1 expression.
Bing QIN ; Bo XIAO ; Ting JIANG ; Huan YANG
Journal of Central South University(Medical Sciences) 2012;37(7):675-681
OBJECTIVE:
To investigate the effect of miR-590-5p on the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in apoptotic human umbilical vein endothelial cells (HUVECs) induced by ox-LDL, and to explore the role of miR-590-5p in modulating HUVECs apoptosis.
METHODS:
HUVECs were exposed to ox-LDL (50 μg/mL) for 0 to 48 h. Apoptosis was detected by Annexin V-FITC stain and was distinguished from necrosis by propidium iodide (PI) staining. The relative expression level of miR-590-5p in HUVECs was analyzed using real-time quantitative PCR (RT-qPCR). HUVECs were transfected with miR-590-5p mimics or miRNA mimics control followed by 50 μg/mL ox-LDL stimulation for 48 h. LOX-1 mRNA and protein were measured by RT-qPCR and Western blot, and apoptosis in HUVECs was analyzed by flow ctyometry after Annexin V-FITC/PI double stain.
RESULTS:
Incubation of HUVECs with 50 μg/mL ox-LDL for 0 to 48 h resulted in a time-dependent induction of apoptotic cell death and down-regulation of miR-590-5p. Transfection of miR-590-5p mimics suppressed LOX-1 expression at both mRNA and protein levels, leading to a reduction of ox-LDL-induced apoptosis in HUVECs.
CONCLUSION
MiR-590-5p protects endothelial cells from ox-LDL induced apoptosis by inhibiting the expression of LOX-1.
Apoptosis
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genetics
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Cells, Cultured
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Human Umbilical Vein Endothelial Cells
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cytology
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Humans
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Lipoproteins, LDL
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pharmacology
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MicroRNAs
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genetics
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metabolism
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RNA, Messenger
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genetics
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metabolism
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Scavenger Receptors, Class E
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genetics
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metabolism
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Transfection
4.Effects of electroacupuncture on the expression of oxidized low-density lipoprotein and its receptors in rats with coronary atherosclerotic heart disease.
Meng LI ; Rong-Lin CAI ; Ling HU ; Zi-Jian WU ; Xu SUN ; Ke-Ming WANG ; Lu HE ; Chuan-Yu PENG
Chinese Acupuncture & Moxibustion 2013;33(9):817-823
OBJECTIVETo explore action mechanism of electroacupuncture for coronary atherosclerotic heart disease (CHD) in order to provide experimental support for clinical acupoint selection.
METHODSAmong sixty clean-grade healthy male Wistar rats, twenty-four cases were randomly selected as a normal control group and an electroacupuncture (EA) preconditioning group, 12 cases in each one. Then rats in the EA preconditioning group and the rest 36 rats were fed with high fat diet for 12 weeks to duplicate the CHD model. When the models were successfully established, the rats were randomly divided into a model control group, an EA group and a medication group, 12 cases in each one. EA was applied with Hwa-to SDZ-IV apparatus in the EA preconditioning group at "Neiguan" (PC 6) and "Xinshu" (BL 15), 1 mA in current intensity, 2 Hz in frequency, 30 min per times, once every other day for 14 weeks. When model was established, the same acupoint and method was used in the EA group for 2 weeks while intragastric administration of atorvastatin mixed suspension, 0.25 mg/kg, once a day, was applied in the medication group for 2 weeks. The content of oxidized low-density lipoprotein (oxLDL) in the serum was tested by double antibody enzyme-linked immunosorbent assay (ELISA) while content of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in coronary arterial tissue was test by western blot method. Expression of LOX-1 mRNA was tested by fluorogenic quantitative polymerase chain reaction (PCR).
RESULTSAfter model was duplicated successfully, the content of oxLDL in the serum and the expression of LOX-1 and its mRNA in coronary arterial tissue in the model control group were increased significantly compared with those in the normal control group (all P < 0.01). Compared with the model control group, the content of oxLDL in the serum and the expression of LOX-1 and its mRNA in coronary arterial tissue in the EA preconditioning group, EA group and medication group were significantly reduced (all P < 0.01).
CONCLUSIONThe electroacupuncture at "Neiguan" (PC 6) and "Xinshu" (BL 15) could effectively reduce the content of oxLDL in the serum and expression of LOX-1 and its mRAN in coronary arterial tissue in CHD rats. The oxidative modificatory low-density lipoprotein and its specific receptor system could be one of the ways to prevention and treatment of acupuncture for CHD.
Animals ; Coronary Disease ; genetics ; metabolism ; therapy ; Disease Models, Animal ; Electroacupuncture ; Humans ; Lipoproteins, LDL ; genetics ; metabolism ; Male ; Rats ; Rats, Wistar ; Scavenger Receptors, Class E ; genetics ; metabolism
5.Value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and LOX-1 mRNA in peripheral mononuclear cells in early diagnosis of acute coronary syndrome.
Jian XU ; Jian-hua ZHU ; Ming-juan SHI
Journal of Southern Medical University 2010;30(12):2749-2751
OBJECTIVETo assess the value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and LOX-1 mRNA expression in peripheral blood mononuclear cells in early diagnosis of acute coronary syndrome (ACS).
METHODSEnzyme-linked immunosorbent assay was used to detect the levels of plasma ox-LDL and LOX-1 in 95 patients with ACS, 60 with stable angina pectoris (SAP) and 40 normal control subjects. The expression of LOX-1 mRNA in peripheral blood mononuclear cells was detected by RT-PCR in the 3 groups.
RESULTSThe levels of ox-LDL, LOX-1 and LOX-1 mRNA in the peripheral blood mononuclear cells were significantly higher in ACS patients than in SAP patients and normal control subjects (P<0.05). In ACS group, the level of plasma ox-LDL was significantly correlated to serum LOX-1 and LOX-1 mRNA expression in peripheral mononuclear cells.
CONCLUSIONThe level of plasma soluble LOX-1 and LOX-1 mRNA in peripheral mononuclear cells are significantly increased in ACS, and when combined, they provide a useful means for detecting ACS in the prophase.
Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Early Diagnosis ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Scavenger Receptors, Class E ; blood
6.Lentivirus-mediated LOX-1-RNA interference attenuates oxidative stress-induced apoptosis in myocardial cells.
Bin LIU ; Jiacheng HUANG ; Yingchun ZHOU ; Xuegang SUN ; Wenbi ZENG ; Xing LI ; Shuwen ZANG ; Wenwen HAO
Journal of Southern Medical University 2012;32(2):165-168
OBJECTIVETo construct a lectin-like oxidized low-density lipoprotein receptor (LOX-1) RNA interference (RNAi) lentivirus and explore the role of LOX-1 in H(2)O(2)-induced apoptosis of rat myocardial cells.
METHODSLOX-1 shRNA sequence was synthesized and cloned into pLentiLox3.7 (pLL3.7) lentiviral vector to construct the lentiviral vector pLL3.7-LOX1. The lentiviral vectors (pLL3.7 and pLL3.7-LOX1) and the packaging vectors dR8.9 and VSVG were co-transfected into 293FT cells for packaging the lentivirus. H9C2 myocardial cells were infected by the lentiviruses to observe the inhibitory rate of LOX-1 on H(2)O(2)-induced apoptosis of H9C2 cells by RT-PCR, CCK-8, and Hochest33258 staining.
RESULTSDouble restriction enzyme digestion and DNA sequencing confirmed correct insertion of the sequence. Suppression of LOX-1 by the lentivirus attenuated H(2)O(2)-induced cell viability reduction and apoptosis in the myocardial cells (P<0.01).
CONCLUSIONLOX-1 activation may play an important role in H(2)O(2)-induced apoptosis of rat myocardial cells.
Animals ; Apoptosis ; physiology ; Cells, Cultured ; Genetic Vectors ; genetics ; Hydrogen Peroxide ; Lentivirus ; genetics ; Myocytes, Cardiac ; cytology ; Oxidative Stress ; RNA Interference ; RNA, Small Interfering ; genetics ; Rats ; Scavenger Receptors, Class E ; genetics
7.Effect of IL-10 on LOX-1 expression of peripheral blood monocytes in patients with acute coronary syndrome.
Jian-gang WANG ; Zhong-shu LIANG ; Kan YANG ; Zhi-jun HUANG ; Jing-le LI
Journal of Central South University(Medical Sciences) 2008;33(2):169-173
OBJECTIVE:
To determine the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with acute coronary syndromes (ACS),and to further explore the effect of anti-inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1.
METHODS:
Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme-linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The expression of LOX-1 protein and mRNA in the monocytes was examined by Western blot and reverse transcriptase PCR (RT-PCR).
RESULTS:
Compared with the healthy controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly upregulated in the isolated monocytes from ACS patients, which could be downregulated by IL-10 (20 microg/L, 3 h) (P<0.01).
CONCLUSION
The effect of anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism resulting in plaque stabilization via the decreased LOX-1 expression of peripheral monocytes in ACS patients.
Acute Coronary Syndrome
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blood
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Aged
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Cells, Cultured
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Female
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Humans
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Interleukin-10
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metabolism
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pharmacology
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Male
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Middle Aged
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Monocytes
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cytology
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metabolism
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RNA, Messenger
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biosynthesis
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genetics
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Scavenger Receptors, Class E
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biosynthesis
;
genetics
8.Fluvastatin prevents renal injury and expression of lactin-like oxidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia.
Yong-hui YU ; Yi WANG ; Bo DONG ; Shu-zhen SUN ; Yao CHEN ; Xiao-hui MENG ; Zhong-zhi LIU
Chinese Medical Journal 2005;118(8):621-626
BACKGROUNDLipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.
METHODSTwenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin [10 mg.kg(-1).d(-1)]. After 16 weeks, serum total cholesterol (TC), low-density lipoprotein (LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using (99m)Tc-DTPA single photon emission computed tomograph ((99m)Tc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.
RESULTSHigh cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits.
CONCLUSIONSFluvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.
Animals ; Cholesterol ; blood ; Creatinine ; blood ; Fatty Acids, Monounsaturated ; pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Hypercholesterolemia ; drug therapy ; metabolism ; pathology ; Immunohistochemistry ; Indoles ; pharmacology ; Kidney ; drug effects ; pathology ; Male ; RNA, Messenger ; analysis ; Rabbits ; Receptors, LDL ; analysis ; genetics ; Receptors, Oxidized LDL ; Scavenger Receptors, Class E ; Tomography, Emission-Computed, Single-Photon
9.Intervention of Tongxinluo capsule against vascular lesion of atherosclerosis and its effect on lectin-like oxidized low density lipoprotein receptor-1 expression in rabbits.
Yong-hui YU ; Xiao-qun XU ; Yi WANG ; Shu-zhen SUN ; Yao CHEN
Chinese journal of integrative medicine 2006;12(1):32-36
OBJECTIVETo investigate the prevention by Tongxinluo capsule (TXL) of vascular lesions and its effect on the levels of protein and gene expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of vascular wall in rabbits with atherosclerosis (AS), and to explore its possible mechanism against AS.
METHODSAS models were established by feeding New Zealand white rabbits with high-cholesterol diet, and 24 immature rabbits were randomly divided into the control group, model group and treated group (treated with TXL capsule). The indexes of total cholesterol (TC) and low density lipoprotein (LDL) levels were measured at the 16th week. The intima thickness and the plaque area of abdominal aorta were quantitatively analyzed by pathological morphological analysis, the expression of macrophage and smooth muscle cell (SMC) in intima were detected by immunohistochemical method and histologic segments were stained by Hematoxilin-Eosin (HE) to identify the degree of atherosclerotic lesion in the model group and the prevention by TXL. The LOX-1 gene and protein expression in abdominal aorta was detected by semi-quantitative RT-PCR and immunohistochemistry, respectively.
RESULTSIn the model group, the levels of TC and LDL were significantly elevated, aortic intima thickened extensively, the intima area enhanced, and macrophages expression increased; the levels of LOX-1 gene and protein expression was up-regulated in endothelium and neo-intima of the abdominal aorta. The treatment with TXL reduced blood lipids, attenuated arterial intimal proliferation, markedly inhibited the expression of macrophage and excessively expressed the level of LOX-1.
CONCLUSIONTXL has an inhibitory effect on blood lipids, and it can prevent the occurrence of vascular lesion and cure its development, and its protection against AS was possibly associated with a crucial endothelial protective action through lowering the expression of LOX-1 in vascular walls.
Actins ; metabolism ; Animals ; Aorta, Abdominal ; metabolism ; pathology ; Atherosclerosis ; metabolism ; pathology ; prevention & control ; Drugs, Chinese Herbal ; pharmacology ; Immunohistochemistry ; Lipids ; blood ; Macrophages ; pathology ; Male ; Muscle, Smooth, Vascular ; pathology ; RNA, Messenger ; analysis ; Rabbits ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class E ; genetics ; metabolism
10.Effect of Antrodia cinnamomea on gene expression related to aortal endothelial injury in rats with hyperlipidemia.
Jie QI ; Yun TAO ; Jun ZHANG ; Jian FU
China Journal of Chinese Materia Medica 2014;39(9):1670-1674
OBJECTIVETo investigate the effect of Antrodia cinnamomea on gene expression related to aortal endothelial injury of rats with hyperlipidemia.
METHODFifty SD rats were randomly divided into five groups: the normal control group (NG), the model group (MG), the antrodia cinnamomea groups of low, middle and high doses (AC-LG, AC-MG, AC-HG, 250, 500, 1 000 mg x kg(-1)). The rats were fed with high-fat diets to establish the hyperlipidemia model. After the drug administration for 10 weeks, their serum lipid, SOD, MDA and ox-LDL, LOX-1, P38 MAPK and NF-kappaB mRNA and protein expression were respectively determined, and the aortal endothelial injury was observed under electron microscope.
RESULTIn the model group, the contents of TC, TG and LDL-C significant increased (P < 0.01), whereas the content of HDL-C significant decreased (P < 0.01). Compared with the model group, both the AC-M group and the AC-H group showed reduction in endothelial injury and significant decrease in the content of TC, TG and LDL-C (P < 0.05 or P < 0.01). The content of HDL-C increased, but with no significant difference. SOD activity in serum remarkably increased (P < 0.05 or P < 0.01), MDA and ox-LDL levels dramatically decreased (P < 0.05 or P < 0.01).
CONCLUSIONA. cinnamomea can alleviate endothelial lipid injury by inhibiting the expressions of LOX-1, P38MAPK and NF-kappaB in aorta and better protect aortal endothelial cells from oxidative lipid injury.
Animals ; Antrodia ; chemistry ; Aorta ; drug effects ; metabolism ; ultrastructure ; Atherosclerosis ; blood ; genetics ; prevention & control ; Biological Products ; pharmacology ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Endothelium, Vascular ; drug effects ; metabolism ; pathology ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; drug effects ; Hyperlipidemias ; blood ; genetics ; prevention & control ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Microscopy, Electron ; NF-kappa B ; blood ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class E ; blood ; genetics ; metabolism ; Superoxide Dismutase ; blood ; Triglycerides ; blood ; p38 Mitogen-Activated Protein Kinases ; blood ; genetics ; metabolism