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1.
高密度脂蛋白抗氧化作用及意义 总被引:1,自引:0,他引:1
血浆高密度脂蛋白除参与胆固醉逆向转运以外,还具有抗氧化等多种重要生理功能。高密度脂蛋白含有的载脂蛋白、磷脂、二乙基对硝基苯磷酸脂酶、血小板激活因子乙酰水解酶、卵磷脂胆固醇酰基转移酶以及清道夫受体BI、ATP结合转运子等其它蛋白成份,不仅具有螯合过渡金属离子、中断脂质氧化反应的作用,还具有摄取、转运、酶解等清除脂质氧化产物、调节抗氧化剂的作用,因而可对抗脂质氧化修饰和动脉粥样硬化的发生。 相似文献
2.
HDL抗动脉粥样硬化的作用 总被引:1,自引:0,他引:1
高密度脂蛋白(HDL)逆向转运胆固醇并以此发挥其经典的抗动脉粥样硬化(AS)作用.除此之外,HDL还具有保护内皮细胞、抑制白细胞粘附、调节血凝与纤溶、抑制血小板聚集与活化、抗脂质氧化等生物学活性,且HDL还可通过胆固醇逆向转运作用以外的多种途径发挥抗AS作用. 相似文献
3.
HDL抗动脉粥样硬化的作用 总被引:1,自引:0,他引:1
高密度脂蛋白(HDL)逆向转运胆固醇并以此发挥其经典的抗动脉粥样硬化(AS)作用。除此之外,HDL还具有保护内皮细胞、抑制白细胞粘附、调节血凝与纤溶、抑制血小板聚集与活化、抗脂质氧化等生物学活性,且HDL还可通过胆固醇逆向转运作用以外的多种途径发挥抗AS作用。 相似文献
4.
高密度脂蛋白抗动脉粥样硬化的研究进展 总被引:18,自引:0,他引:18
低水平的血浆高密度脂蛋白胆固酵(HDL-C)是冠心病的独立危险因子,HDL—C与冠心病的发病呈负相关。高密度脂蛋白(HDL)通过多种机制发挥其抗动脉粥样硬化的作用:它具有抗低密度脂蛋白氧化修饰的作用,减少脂质的摄取沉积;参与胆固醇的逆向转运,促进胆固醇从血管壁排出,将其运送至肝脏清除,并增加粥样硬化斑块的稳定性,减少斑块破裂。此外,它还能保护内皮屏障功能,介导内皮依赖性舒张,并降低粘附分子的表达,具有冠脉保护作用。本文主要阐述HDL抗动脉粥样硬化机制研究的新进展。 相似文献
5.
高密度脂蛋白(HDL)在体内经过髓过氧化物酶氧化形成不同位点修饰的HDL(ox-HDL),ox-HDL通过损伤内皮细胞、影响胆固醇逆转运过程、促进平滑肌增生等方式降低抗动脉粥样硬化的作用。因此HDL不同位点的氧化修饰及相关功能改变或将为治疗动脉粥样硬化提供新的思路。 相似文献
6.
目的分析不同高脂血症人群血清胆固醇酯转运蛋白水平及其对血浆各脂蛋白间脂质转运的调节作用。方法脂蛋白电泳结合酶显色法分别检测血清各脂蛋白中的甘油三酯含量;酶联免疫吸附试验测定血清胆固醇酯转运蛋白和氧化型低密度脂蛋白水平;分析胆固醇酯转运蛋白与脂质水平间的相关性。结果高甘油三酯组、高胆固醇组、混合组和对照组中胆固醇酯转运蛋白水平分别为1.89±1.32、2.37±1.30、2.33±1.73和1.58±1.00 mg/L,与对照组比较,高甘油三酯组变化无显著性(P>0.05),高胆固醇组(P<0.01)和混合组均升高(P<0.05)。高脂血症人群高密度脂蛋白中胆固醇/甘油三酯比值降低;高甘油三酯组和混合组低密度脂蛋白中甘油三酯/胆固醇比值升高,高胆固醇组无差别,其中高甘油三酯组变化程度最大,混合组次之,高胆固醇组最小;且胆固醇酯转运蛋白水平与上述比值相关。高脂血症人群血清氧化型低密度脂蛋白水平升高,与低密度脂蛋白中甘油三酯/胆固醇比值高度呈正相关。结论高脂血症人群胆固醇酯转运蛋白水平升高,促进了脂蛋白间脂质转运,使高密度脂蛋白和低密度脂蛋白脂质组成发生变化,促进了动脉粥样硬化的发生和发展。 相似文献
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8.
吴满平 《中国动脉硬化杂志》2008,16(6):421-423
高密度脂蛋白重构是细胞外间隙产生含少量脂质或无脂质的载脂蛋白AI的重要途径。"细胞核肝X受体-ATP结合盒转运体A1-载脂蛋白AI"通路对调控细胞胆固醇流出、调节细胞内环境稳定是十分重要的,并在体内胆固醇逆向转运起始步骤—细胞胆固醇流出中起关键作用。炎症状态下高密度脂蛋白重构增强,这对机体急性相反应是一种保护作用,慢性炎症及持续增强高密度脂蛋白重构导致高密度脂蛋白分解加强,血浆高密度脂蛋白降低,具有潜在危害性。 相似文献
9.
载脂蛋白M是新近发现的一种脂质转运蛋白,是高密度脂蛋白的组成成分,特异表达于肝脏和肾脏。研究表明,载脂蛋白M具有抗动脉粥样硬化作用,其相关机制可能涉及胆固醇逆转运、炎症以及糖尿病防治等。 相似文献
10.
大量临床流行病学资料证实血浆低密度脂蛋白胆固醇水平升高及高密度脂蛋白胆固醇水平降低均是动脉粥样硬化性心血管疾病的独立危险因素。在生理过程中抑制胆固醇酯转运蛋白可以升高血浆高密度脂蛋白胆固醇水平,理论上可能具有抗动脉粥样硬化的作用。然而迄今为止,调节胆固醇酯转运蛋白的动物模型和临床研究结果不尽一致,以抑制胆固醇酯转运蛋白为基础的相关药物治疗选择带来了不确定性。文章从胆固醇酯转运蛋白在脂质代谢中的生理作用、部分动物研究中与动脉粥样硬化的关系以及临床应用对动脉粥样硬化性心血管疾病的影响等方面的最新研究进展进行综述。 相似文献
11.
目的观察高血压病患者高密度脂蛋白抗氧化活性有无变化及可能的影响因素。方法纳入33名高血压病患者及32名健康对照者,采用一次性密度梯度超速离心法分离高密度脂蛋白及低密度脂蛋白,体外Cu2 诱导法作脂蛋白氧化,用分光光度法、硫代巴比妥酸法测定高密度脂蛋白抗氧化能力、氧化延迟时间和体外过氧化程度,分光光度仪连续监测法测定血清对氧磷酶1活性。结果高血压病患者与正常对照组比较,高密度脂蛋白抗氧化活性及对氧磷酶1活性下降(P均<0.05),高密度脂蛋白氧化延迟时间、体外过氧化程度差异没有统计学意义;高密度脂蛋白抗氧化活性与对氧磷酶1活性呈正相关,与收缩压、舒张压和总胆固醇浓度呈负相关(r分别为0.317、-0.387、-0.42和-0.259,P均<0.05)。结论高血压病患者高密度脂蛋白抗氧化活性降低可能是易患动脉粥样硬化的重要因素。血压、对氧磷酶1活性等影响高密度脂蛋白抗氧化活性。 相似文献
12.
High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma from fasting donors. 总被引:20,自引:1,他引:20
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V W Bowry K K Stanley R Stocker 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(21):10316-10320
Analysis of untreated fresh blood plasma from healthy, fasting donors revealed that high density lipoprotein (HDL) particles carry most (approximately 85%) of the detectable oxidized core lipoprotein lipids. Low density lipoprotein (LDL) lipids are relatively peroxide-free. In vitro the mild oxidation of gel-filtered plasma from fasting donors with a low, steady flux of aqueous peroxyl radicals initially caused preferential oxidation of HDL rather than LDL lipids until most ubiquinol-10 present in LDL was consumed. Thereafter, LDL core lipids were oxidized more rapidly. Isolated lipoproteins behaved similarly. Preferential accumulation of lipid hydroperoxides in HDL reflects the lack of antioxidants in most HDL particles compared to LDL, which contained 8-12 alpha-tocopherol and 0.5-1.0 ubiquinol-10 molecules per particle. Cholesteryl ester hydroperoxides (CEOOHs) in HDL and LDL were stable when added to fresh plasma at 37 degrees C for up to 20 hr. Transfer of CEOOHs from HDL to LDL was too slow to have influenced the in vitro plasma oxidation data. Incubation of mildly oxidized LDL and HDL with cultured hepatocytes afforded a linear removal of CEOOHs from LDL (40% loss over 1 hr), whereas a fast-then-slow biphasic removal was observed for HDL. Our data show that HDL is the principal vehicle for circulating plasma lipid hydroperoxides and suggest that HDL lipids may be more rapidly oxidized than those in LDL in vivo. The rapid hepatic clearance of CEOOHs in HDL could imply a possible beneficial role of HDL by attenuating the build-up of oxidized lipids in LDL. 相似文献
13.
Navab M Berliner JA Subbanagounder G Hama S Lusis AJ Castellani LW Reddy S Shih D Shi W Watson AD Van Lenten BJ Vora D Fogelman AM 《Arteriosclerosis, thrombosis, and vascular biology》2001,21(4):481-488
Oxidation of low density lipoprotein (LDL) phospholipids containing arachidonic acid at the sn-2 position occurs when a critical concentration of "seeding molecules" derived from the lipoxygenase pathway is reached in LDL. When this critical concentration is reached, the nonenzymatic oxidation of LDL phospholipids produces a series of biologically active, oxidized phospholipids that mediate the cellular events seen in the developing fatty streak. Normal high density lipoprotein (HDL) contains at least 4 enzymes as well as apolipoproteins that can prevent the formation of the LDL-derived oxidized phospholipids or inactivate them after they are formed. In the sense that normal HDL can prevent the formation of or inactivate these inflammatory LDL-derived oxidized phospholipids, normal HDL is anti-inflammatory. HDL from mice that are genetically predisposed to diet-induced atherosclerosis became proinflammatory when the mice are fed an atherogenic diet, injected with LDL-derived oxidized phospholipids, or infected with influenza A virus. Mice that were genetically engineered to be hyperlipidemic on a chow diet and patients with coronary atherosclerosis, despite normal lipid levels, also had proinflammatory HDL. It is proposed that LDL-derived oxidized phospholipids and HDL may be part of a system of nonspecific innate immunity and that the detection of proinflammatory HDL may be a useful marker of susceptibility to atherosclerosis. 相似文献
14.
OBJECTIVE: Elevated levels of high-density lipoprotein (HDL) cholesterol are inversely related to the risk of cardiovascular disease. The anti-atherosclerotic function of HDL is mainly ascribed to its role in reverse cholesterol transport, and requires the integrity of HDL structure. Experimental evidence suggests that the ability of HDL to promote removal of excess cholesterol from peripheral cells is impaired upon oxidation. On the other hand, tyrosylation of HDL enhances its protective function, suggesting that not all forms of modified lipoprotein may be atherogenic. In the present study we investigated the effect of a mild oxidation of HDL(3) on its function as cholesterol acceptor. METHODS AND RESULTS: A mild oxidative stress (induced by 15 min exposure of HDL(3) to 1 microM Cu(++) or to 15-lipoxygenase) caused the formation of pre-beta-migrating particles. Compared to native lipoprotein, mildly modified HDL(3) induced a significant ATP-binding cassette transporter 1 (ABCA1)-mediated increase of cholesterol and phospholipids efflux from J774 macrophages. This effect was abolished by an inhibitor of ABCA1-mediated lipid efflux (glyburide) and was absent in Tangier fibroblasts. CONCLUSIONS: A mild oxidative modification of HDL(3) may improve its function as cholesterol acceptor, increasing ABCA1-mediated lipid efflux from macrophages, a process that may reduce foam cell formation. 相似文献
15.
Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men 总被引:7,自引:0,他引:7
Kristiina Nyyss nen Elina Porkkala-Sarataho Jari Kaikkonen Jukka T. Salonen 《Atherosclerosis》1997,130(1-2):223-233
Copper-induced plasma lipoprotein oxidation resistance has usually been determined in separated low density lipoprotein (LDL) fractions, that do not contain water-soluble antioxidants present in blood plasma. The aim of this study was to find the main determinants of the measurements of copper-induced lipid oxidation resistance (lag time) in whole serum and plasma total peroxyl radical trapping capacity (TRAP) in a population sample of smoking (n=25) or non-smoking (n=26) middle aged men at high risk of cardiovascular diseases. Smokers had significantly lower plasma ascorbic acid values, but only slightly lower -tocopherol, β-carotene and serum urate values than non-smokers. Plasma ascorbic acid concentration explained 23.5% of the lag time variation (standardized regression coefficient β=0.48; P=0.004) in smokers and 5.6% in non-smokers. Serum urate concentration was the strongest determinant of lag time in non-smokers (β=0.64, P<0.001). In addition, serum albumin, lipid standardized -tocopherol and serum high density lipoprotein (HDL) cholesterol entered the multivariate regression model for lag time. For plasma TRAP, only urate and ascorbic acid entered the multivariate regression model. Lag times in serum and in isolated very low density lipoprotein (VLDL) and LDL fraction did not correlate, but the maximal rate of these reactions correlated significantly. These results confirm that lipid peroxidation resistance in serum or plasma are associated with ascorbic acid, urate, -tocopherol, albumin and HDL concentrations. The measurement of lipid oxidation resistance in whole serum might be more physiological than in isolated lipoprotein fraction, as the effects of water-soluble antioxidants are not artificially removed. 相似文献
16.
Zago V Sanguinetti S Brites F Berg G Verona J Basilio F Wikinski R Schreier L 《Atherosclerosis》2004,177(1):203-210
The high incidence of atherosclerosis in women after menopause is associated with a risk pattern including an increase in low density lipoprotein (LDL), even though high density lipoprotein (HDL) cholesterol levels tend to be maintained or slightly decreased. Since estrogens are considered potent antioxidants, an increase in lipid peroxidation and formation of reactive oxygen species would be expected after menopause. If HDL becomes oxidized, the ability to protect LDL against oxidation may be impaired. In postmenopausal women there are scarce reports concerning HDL oxidability and no data about its antioxidant activity. We studied copper-induced oxidation and conjugated dienes formation in HDL isolated from 58 women, 30 postmenopausal (PMW) and 28 premenopausal (PreMW). None presented diabetes or cardiovascular disease and none was receiving hormonal, hypolipidemic or antioxidant therapy either. In order to evaluate the effect of HDL on LDL oxidation we isolated LDL and HDL from the same subject and assessed copper-induced LDL oxidation in the presence of HDL, followed by thiobarbituric acid-reactive substances determination. Relationships with HDL chemical composition, alpha-tocopherol content, cholesteryl ester transfer protein (CETP) and paraoxonase activity (PON) were investigated. HDL chemical composition in PMW exhibited triglyceride enrichment when compared to PreMW (p <0.05). alpha-Tocopherol content and CETP activity were similar in both groups. However, CETP activity correlated positively with HDL triglyceride and negatively with HDL cholesterol percentage (r=0.44, p <0.01 and r=-0.32, p <0.05, respectively). Paraoxonase activity did not show differences between PMW and PreMW. When evaluating HDL oxidability, PMW revealed a shorter lag time in comparison to PreMW, even after adjustment for age, p <0.05. Moreover, when the effect of HDL on LDL oxidation was evaluated, HDL from PMW showed a reduction in its ability to inhibit LDL oxidation, compared to PreMW (p <0.05). In addition, the extent of inhibition of LDL oxidation by HDL was positively correlated with HDL resistance to oxidation (r=0.27, p <0.05). After women classification by paraoxonase phenotype, HDL ability to protect LDL against oxidation remained reduced only in PMW belonging to the PON QR phenotype, in comparison to PreMW QR. These results suggest that HDL from PMW exhibits impairment in its antioxidant ability, which is associated to a decreased HDL resistance to oxidation. In turn, this was related to triglyceride enrichment of HDL particles. All these alterations were independent from HDL cholesterol plasma levels. 相似文献
17.
Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may Be due to the abnormal composition of HDL. 总被引:6,自引:0,他引:6
M S Gowri D R Van der Westhuyzen S R Bridges J W Anderson 《Arteriosclerosis, thrombosis, and vascular biology》1999,19(9):2226-2233
High plasma triglyceride concentrations in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown that the high density lipoprotein (HDL) composition is abnormal in type 2 diabetic subjects. One study has shown that HDL (lipoprotein A-I) isolated from subjects with non-insulin-dependent diabetes mellitus exhibits a decreased capacity to induce cholesterol efflux. The current study examined the effect of HDL(2) and HDL(3) subfractions from poorly controlled type 2 diabetic and control subjects on THP-1 macrophage-mediated low density lipoprotein (LDL) oxidation. The composition and protective effects of HDL(2), but not of HDL(3), differed significantly between control and diabetic subjects. HDL(2) from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL(2) inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (P<0.05) more than did diabetic HDL(2) in both the fasting and postprandial state. In addition, HDL(2) from diabetics did not protect against apolipoprotein B-100 fragmentation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presence of LDL, was extensive in HDL(2) from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL(2) (r=-0.673, P<0.05) in diabetic but not in control subjects. HDL(2)-associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL(2) in control (r=0.872, P<0.002) but not in diabetic subjects. In conclusion, compositional alterations in HDL(2) from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties. 相似文献
18.
Changes in plasma lipoproteins in acute malaria 总被引:3,自引:0,他引:3
Plasma lipid and lipoprotein concentrations were monitored in 16 patients with acute malaria. Plasma high density lipoprotein (HDL) levels decreased dramatically during the first 3 d after diagnosis to around 0.2 mmol l-1 (reference range 0.8-1.6 mmol l-1). The low HDL levels were related to parasitaemia, and rapidly recovered after successful therapy. Plasma triglyceride concentrations were moderately increased and plasma low density lipoprotein (LDL) cholesterol concentrations decreased during the course of infection. The mechanisms underlying the selective and pronounced decline in HDL cholesterol concentration remain obscure, but the reproducible phenomenon may be useful as an additional diagnostic tool in suspected malaria infection. 相似文献
19.
脂质对大鼠肝星状细胞低密度脂蛋白、高密度脂蛋白受体的影响 总被引:2,自引:0,他引:2
目的研究脂质(甘油三酯和极低密度脂蛋白)对大鼠HSC低密度脂蛋白(low-densitylipoprotein,LDL)、高密度脂蛋白(high-densitylipoprotein,HDL)受体的影响。方法用链霉蛋白酶和胶原酶原位灌流,Nycodenz密度梯度离心分离大鼠HSC;应用125I-LDL和125I-HDL3配体进行放射性配基结合实验测定脂质对HSC膜LDL、HDL受体的影响。结果HSC膜表面存在LDL、HDL受体;脂质可增加LDL受体对LDL的亲合力,但降低HDL受体对HDL3的亲合力。结论HSC膜上的LDL、HDL受体对脂蛋白代谢及胆固醇的调节有重要作用,为阐明脂肪肝肝纤维化的发生提供了新的实验依据。 相似文献
20.
P Samuel W Kirkendall E J Schaefer B Chin B H Schoenfeld L M Gonasun S Lieberman 《The American journal of cardiology》1988,62(16):1068-1071
The effect of isradipine versus hydrochlorothiazide on the lipid profile of 44 hypertensive patients was investigated in a double-blind, randomized, 2-center trial. Lipid profiles included total cholesterol, serum triglycerides, high density lipoprotein (HDL) cholesterol, HDL subclasses, (HDL2 and HDL3), low density lipoprotein cholesterol, very low density lipoprotein cholesterol, apolipoprotein A-1 and apolipoprotein B. Isradipine had no effect on the lipid profile in short- (4 and 10 week) or long-term (52 week) studies. Hydrochlorothiazide increased serum triglycerides in 11 of 13 patients by a mean of 8% for the group (p less than 0.05) in long-term (52 week) studies, and total cholesterol by a mean of 9 and 16%, respectively (p less than 0.01) in 2 of 13 patients, with no difference in other lipid or lipoprotein parameters in short- or long-term studies. 相似文献