冠心病患者脂联素与氧化型低密度脂蛋白和一氧化氮水平的相关性

血管内皮损伤、炎症反应等在冠心病(CHD)患者动脉粥样硬化(AS)发展的过程中起着举足轻重的作用.血浆脂联素(APN)可以抑制内皮细胞黏附因子的表达、平滑肌细胞的增殖和迁移、巨噬细胞向泡沫细胞的转变过程而使炎症反应终止,达到有效的抗AS作用,对血管内皮起到保护效果.低密度脂蛋白(LDL),特别是经过氧化修饰后的氧化型LDL(ox-LDL)是可直接反映AS斑块稳定状况的标志.一氧化氮(NO)是血管内皮细胞释放的血管活性物质,在调节和维持内皮功能方面有重要作用.本研究旨在分析APN与ox-LDL、NO之间的相关性,为冠心病的诊治提供依据.     

凝集素样氧化型低密度脂蛋白受体-1与动脉粥样硬化关系的研究进展

凝集素样氧化型低密度脂蛋白受体-1（lectin-like oxidized low-density lipoprotein receptor-1,LOX-1）是内皮细胞上氧化型低密度脂蛋白特异性受体,可介导内皮细胞活化、损伤和凋亡,平滑肌细胞和巨噬细胞内脂质聚集,活化血小板促进血栓形成,并增加斑块不稳定性,促进动脉粥样硬化（atherosclerosis,AS）的发生发展。而抑制LOX-1表达可减弱AS病变,提示LOX-1可能成为防治AS的分子靶点。本文就LOX-1与AS的关系作一综述。     

“氧化型低密度脂蛋白—凝集素样氧化型低密度脂蛋白受体1—活性氧”信号通路参与泡沫细胞的形成

动脉粥样硬化是多因素引起的,以动脉壁内脂质的沉积甚至粥样斑块的形成为特征的慢性血管炎症性疾病.巨噬细胞内胆固醇的堆积和泡沫细胞的形成是早期动脉粥样硬化形成的标志.然而,泡沫细胞形成的确切机制尚未完全阐明.于此,我们推测氧化型低密度脂蛋白(oxidized low density lipoprotein,ox-LDL),凝集素样氧化型低密度脂蛋白受体1(lectin-like oxidized low density lipoprotein receptor-1,LOX-1)和活性氧(reactive oxygen species,ROS)组成了一个促进泡沫细胞形成的"信号通路",在泡沫细胞的形成乃至诱导动脉粥样硬化发生中起始动作用.在这一通路中,氧化型低密度脂蛋白,这种经过氧化修饰的低密度脂蛋白,是"激活子";凝集素样氧化型低密度脂蛋白受体1,作为内皮细胞上的氧化型低密度脂蛋白的主要受体是信号"转导子";活性氧,这氧化型低密度脂蛋白与凝集素样氧化型低密度脂蛋白受体1结合后的直接产物是"催化子"和"诱导剂".     

血凝素样氧化低密度脂蛋白受体-1

血凝素样氧化低密度脂蛋白受体-1（LOX-1）是内皮细胞摄取氧化低密度脂蛋白（ox-LDL）的特异性受体。高脂血症、氧化应激等多种因素可以促进LOX-1的表达。LOX-1表达通过诱导各种黏附分子和炎症因子的表达、激活蛋白激酶、诱导细胞凋亡等途径促进平滑肌细胞和巨噬细胞吞噬脂质,并转化为泡沫细胞,促进动脉粥样硬化斑块的形成。     

不同类型急性脑梗死患者血清ox-LDL水平变化及临床意义

近年的研究结果发现,氧化低密度脂蛋白(ox-LDL)在动脉粥样硬化性心脑血管疾病的发生发展中起着十分重要的作用.ox-LDL是LDL经氧化修饰后形成,被巨噬细胞摄取的速度是正常LDL-C的数倍乃至数十倍,从而加速了泡沫细胞的形成[1],进一步破坏血管内皮细胞,引起平滑肌的增生和斑块的形成及增厚,促进了血栓形成而造成动脉血栓性脑梗死.     

LOX-1在动脉粥样硬化中的细胞生物学效应及药物治疗新进展

动脉粥样硬化（AS）是一种血管慢性炎症性病变,低密度脂蛋白、氧化型低密度脂蛋白和其他修饰型的脂蛋白在血管内膜下的滞留和聚积被认为是AS的起始因素。凝集素样氧化型低密度脂蛋白受体（LOX）-1在AS的发生、发展中起重要作用,介导了多种信号对血管内皮细胞的刺激,是AS斑块形成的起始因素之一。近年来,不断有新的证据发现LOX-1与细胞外不同配体的相互作用及细胞内效应,并发现多种药物通过抑制LOX-1产生抗AS的作用。本文将着重阐述近年来LOX-1在AS发生、发展中的细胞生物学效应与相关药物治疗新进展。     

血凝素样氧化低密度脂蛋白受体-1

血凝素样氧化低密度脂蛋白受体-1(LOX-1)是内皮细胞摄取氧化低密度脂蛋白(ox-LDL)的特异性受体.高脂血症、氧化应激等多种因素可以促进LOX-1的表达.LOX-1表达通过诱导各种黏附分子和炎症因子的表达、激活蛋白激酶、诱导细胞凋亡等途径促进平滑肌细胞和巨噬细胞吞噬脂质,并转化为泡沫细胞,促进动脉粥样硬化斑块的形成.     

植物血凝素样氧化低密度脂蛋白受体-1与动脉粥样硬化

动脉粥样硬化(AS)是由一系列细胞及分子参与的炎症反应性疾病,在AS发生发展的过程中氧化低密度脂蛋白(ox-LDL)发挥了极其重要的作用。其主要通过2种机制促进AS病变进展:一是通过巨噬细胞的清道夫受体进入细胞,促进细胞的泡沫化,进而泡沫细胞堆积,促进血管内壁脂纹形成;二是引起     

Lox-经ox-LDL介导致动脉粥样硬化机制的研究进展

血凝素样氧化低密度脂蛋白受体1(Lox-1)通过介导ox-LDL信号途径而导致血管内皮功能障碍、泡沫细胞形成及凋亡、炎性介质及基质金属蛋白酶的分泌,在动脉粥样硬化(AS)     

氧化低密度脂蛋白诱导血管内皮细胞损伤的条件培养基对血管平滑肌细胞增殖的作用

目的观察氧化低密度脂蛋白（OX—LDL）损伤血管内皮细胞（VEC）的条件培养基对血管平滑肌细胞（VSMC）生长状态的影响。方法在培养的大鼠胸主动脉平滑肌细胞上，分别采用MTT染色法、流式细胞术及增殖细胞核抗原免疫组化方法等，检测OX—LDL诱导VEC损伤的条件培养基对VSMC生长率、细胞周期及PCNA表达的影响。结果OX—LDL可呈浓度依赖性损伤VEC的形态、减少上清液中NO含量、升高上清液中ET-1含量。终浓度为1001μg,／ml的ox-LDL与VEC共同孵育24h制备的条件培养基，能明显促进VSMC生长、提高PCNA表达及增加细胞周期S期细胞数。结论血管内皮细胞受到OX—LDL损伤时，制备的条件培养基能促进血管平滑肌细胞增殖，这可能是氧化低密度脂蛋白致动脉粥样硬化形成的原因之一。     

Oxidized LDL,LOX-1 and Atherosclerosis

An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for genesis of atherosclerosis. Ox-LDL plays a more important role in the genesis and progression of atherosclerosis than the native LDL. Ox-LDL leads to endothelial dysfunction leading to expression of adhesion molecules and recruitment of monocyte in subendothelial space. Ox-LDL is taken up by macrophages via scavenger receptors, such as SR-A1, SR-A2 and LOX-1. Lately, LOX-1, a type II membrane protein receptor of ox-LDL, has gained much importance in relation to effects of ox-LDL on endothelial biology. Endothelial cells primarily express LOX-1 as receptor for ox-LDL and ox-LDL has been shown to upregulate expression of LOX-1. In addition, ox-LDL promotes the growth and migration of smooth muscle cells, monocytes/macrophages and fibroblasts. In this review we discuss the role of ox-LDL and LOX-1 in genesis and progression of atherosclerosis.     

Angiotensin II increases the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway

BACKGROUND: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a membrane protein that can act as a surface endocytosis receptor for oxidized LDL (ox-LDL). As increased cellular uptake of ox-LDL by macrophages and activated smooth muscle cells may transform these cells into foam cells, potential interactions among LDL oxidation, ox-LDL uptake, and regulators of vascular smooth muscle cell function are of obvious interest. The objective of this study was to examine the effect of angiotensin II (AII) on the expression of LOX-1 and ox-LDL degradation in human vascular smooth muscle cells (VSMC) METHODS: We performed in vitro experiments in a human VSMC line (T/G HA-VSMC) derived from normal aortic VSMC, using standards methods. RESULTS: We found that AII (10(-7) mol/L) increased the expression of LOX-1 (approximately 2.5-fold, P < .0001) in association with higher degradation of ox-LDL by HA-SMC (from 4019 +/- 529 ng/mg cell protein to 6207 +/- 287 ng/mg cell protein; P = .0033). AII also increased the expression of 12-lipoxygenase (12-LO) and 15-lipoxygenase (15-LO) by approximately 2.2-fold (P = .03) and approximately 3-fold (P = .006), respectively. In addition, AII (10(-7) mol/L) increased the release of 12- and 15-hydroxyeicosatetraenoic acid from VSMC within 10 min approximately 3-fold (P = .03) and 50% (P < .05), respectively. CONCLUSIONS: Our study findings provide evidence that angiotensin II upregulates LOX-1 and 12-LO and 15-LO expression in human VSMC, thereby potentially providing mechanisms for both accelerated LDL oxidation within the cell and the internalization of exogenous ox-LDL, two processes that could increase the susceptibility of human VSMC to further transformation into foam cells.     

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in atherogenesis.

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a type-II membrane protein belonging to the C-type lectin family molecules, which can act as a cell surface endocytosis receptor for atherogenic oxidized LDL (Ox-LDL). LOX-1 is synthesized as a 40 kDa precursor protein with N-linked high mannose-type carbohydrate, which is further glycosylated and processed into a 50 kDa mature form. LOX-1 expression is not constitutive but can be induced by proinflammatory, oxidative, and mechanical stimuli. In addition to endothelial cells, macrophages and activated vascular smooth muscle cells express LOX-1. In vivo, endothelial cells covering early atherosclerotic lesions and macrophages and smooth muscle cells accumulated in the intima of advanced atherosclerotic plaques express LOX-1. LOX-1 is cleaved at membrane proximal extracellular domain by some protease activities and released from the cell surface. Measurement of soluble LOX-1 in vivo may provide novel diagnostic strategy for the evaluation and prediction of atherosclerosis and vascular diseases.     

Diabetic vasculopathy and the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)

Type 2 diabetes is associated with an increased incidence of coronary heart disease and cardiovascular complications. One crucial step in the initiation and progression of atherosclerosis is the unregulated uptake of oxidized low-density lipoprotein (oxLDL) by vascular wall components through scavenger receptors. Identification of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) as the major receptor for oxLDL in endothelial cells has provided a new clue to the mechanisms involved in oxLDL accumulation in the vessel wall. This receptor, by facilitating the uptake of oxLDL, induces endothelial dysfunction and mediates numerous oxLDL-induced proatherogenic effects. Besides endothelial cells, LOX-1 is also expressed by smooth muscle cells and macrophages. In these cells, LOX-1 may function as a scavenger receptor and promote foam cell formation. Notably, LOX-1 is induced by multiple stimuli relevant to atherogenesis and inflammation and is up-regulated in various proatherogenic conditions, including diabetes. As such, activation of vascular cells by oxLDL through LOX-1 may be relevant to the development and progression of human diabetic vasculopathy. This review summarizes recent advances related to the role of LOX-1 in atherosclerosis, its regulation by metabolic and inflammatory factors relevant to diabetes and the impact of these factors on LOX-1-mediated proatherogenic events linked to diabetic vasculopathy.     

Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy

Low-density lipoprotein (LDL)-cholesterol is important for cellular function, but in high concentrations, it can lead to atheroma formation. Over the past several decades, it has become abundantly evident that the oxidized form of LDL-cholesterol (ox-LDL) is more important in the genesis and progression of atherosclerosis than native unmodified LDL-cholesterol. Ox-LDL leads to endothelial dysfunction, an initial step in the formation of an atheroma. Ox-LDL acts via binding to a number of scavenger receptors (SR), such as SR-A1, SR-A2 and lectin-like oxidized low-density lipoprotein receptor (LOX-1). Ox-LDL can upregulate expression of its own receptor LOX-1 on endothelial cells and activate these cells. In addition, ox-LDL promotes the growth and migration of smooth muscle cells, monocytes/macrophages and fibroblasts. Ox-LDL also leads to the generation of reactive oxygen species that in physiologic concentrations combat invasion of the body by noxious agents, but when in excess, can lead to a state of oxidative stress. There is evidence for the presence of oxidative stress in a host of conditions such as atherosclerosis and aging. In this review, we discuss the role of oxidative stress, ox-LDL and LOX-1 in atherogenesis and the reasons why the traditional approaches to limit oxidant stress have not been successful.     

LOX-1 and Obesity

Obesity is one of the most common lifestyle-related diseases. Being closely associated with insulin resistance, hypertension and dyslipidemia, it is also a component of metabolic syndrome and is involved in the development of atherosclerosis and cardiovascular and renal ailments. Obesity is also accompanied with a state of chronic inflammation. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a receptor for oxidized low density lipoprotein (ox-LDL), is expressed not only in endothelial cells, but also in macrophages, vascular smooth muscle cells, platelets and adipocytes. LOX-1 binds multiple ligands, has diverse physiological functions and plays a critical role in the signal transduction. It may well turn out to be a key, or very important, factor in the development of hypertension, diabetes mellitus and hyperlipidemia, the most important risk factors for atherosclerosis. In recent studies, LOX-1 upregulation appears to be a vital factor in obesity and its complications. This review summarizes current knowledge of obesity and the relationship between LOX-1 and obesity.     

Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis

Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation. Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis, and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects of LOX-1 blockade.     

Heparin-binding EGF-like growth factor induces expression of lectin-like oxidized LDL receptor-1 in vascular smooth muscle cells

Receptor-mediated endocytosis of oxidized LDL (Ox-LDL) has been implicated in lipid accumulation and vascular cell dysfunction. Lectin-like Ox-LDL receptor-1 (LOX-1) is highly inducible by proinflammatory cytokines, as well as angiotensin II and Ox-LDL in vitro. LOX-1 is expressed in macrophages and smooth muscle cells accumulated in the intima of advanced atherosclerotic plaques in vivo. Here we show that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells, induces LOX-1 expression in cultured bovine aortic smooth muscle cells. HB-EGF (1-100 ng/ml) induced LOX-1 expression, which was peaked between 8 and 16 h after HB-EGF stimulation. HB-EGF-induced expression of LOX-1 was suppressed by ZD1839, an inhibitor of EGF receptor phosphorylation. Both MEK and p38 mitogen-activated protein kinase (MAPK) inhibitors significantly blocked LOX-1 upregulation induced by HB-EGF. Phosphatidylinositol 3-kinase (PI3K) inhibitors also blocked HB-EGF-induced LOX-1 expression. HB-EGF induced phosphorylation of ERK, p38 MAPK and Akt, which were suppressed by ZD1839. Upregulated expression of LOX-1 was associated with enhanced uptake of DiI-labeled Ox-LDL in smooth muscle cells. Taken together, HB-EGF can also act as an inducer of LOX-1 expression and play an integral role in foam cell transformation, cellular dysfunction, and proliferation of smooth muscle cells in atherogenesis.     

New oxidized LDL receptors and their functions in atherogenesis

Oxidized low density lipoprotein (Ox-LDL) appears to play key roles in atherosclerotic progression and plaque rupture. Biological effects of Ox-LDL on vascular cells may, at least in part, be mediated by cell surface receptors for Ox-LDL. Lectin-like oxidized LDL receptor (LOX)-1 and scavenger receptor for phosphatidylserine and oxidized lipoprotein (SR-PSOX) are type II and I membrane glycoprtoeins, respectively, both of which can act as cell-surface endocytosis receptors for atherogenic oxidized LDL (Ox-LDL). LOX-1 expression can dynamically be induced by proinflammatory stimuli, and is detectable in cultured macrophages and activated vascular smooth muscle cells (VSMC), in addition to endothelial cells. LOX-1-dependent uptake of Ox-LDL induced apoptosis of cultured VSMC. In vivo, endothelial cells that cover early atherosclerotic lesions, and intimal macrophages and VSMC in advanced atherosclerotic plaques dominantly express LOX-1. LOX-1 expressed on the cellsurface can be cleaved, in part, and released as soluble molecules, suggesting the diagnostic significance of plasma soluble LOX-1 levels. SR-PSOX appeared to be identical to CXCL16, a novel membrane-anchored chemokine directed to CXCR6-positive lymphocytes, suggesting another role of SR-PSOX as T-cell chemoattractant. In contrast to LOX-1 expressed by a variety of cell types. SR-PSOX expression appeared relatively confined to macrophages in atherogenesis. Taken together, LOX-1 and SR-PSOX may play important roles in atherogenesis and athrosclerotic plaque rupture.