Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Scavenger receptors mediate the endocytosis of chemically modified lipoproteins, such as acetylated low density lipoprotein (Ac-LDL) and oxidized LDL (Ox-LDL), and have been implicated in the pathogenesis of atherosclerosis. The evidence that endothelial cells possess scavenger receptor activity is substantial, and this property is widely used in the isolation of endothelial cells from vascular tissues. In the current study, we have isolated, by expression cloning, the cDNA encoding a novel type of scavenger receptor expressed by endothelial cells (SREC), which mediates the binding and degradation of Ac-LDL. The primary structure of the molecule has no significant homology to other types of scavenger receptors, including the recently cloned endothelial cell Ox-LDL receptor, a member of the C-type lectin family. The cDNA encodes a protein of 830 amino acids with a calculated molecular mass of 85, 735 Da (mature peptide). Chinese hamster ovary cells stably expressing SREC bound 125I-labeled Ac-LDL with high affinity (Kd = 3.0 microg/ml, approximately 1.7 nM) and degraded them via an endocytic pathway. Association of DiII-Ac-LDL were effectively inhibited by Ox-LDL, malondialdehyde-modified LDL, dextran sulfate, and polyinosinic acid, but not by natural LDL and heparin. The cloned receptor has several characteristic domain structures, including an N-terminal extracellular domain with five epidermal growth factor-like cysteine pattern signatures and an unusually long C-terminal cytoplasmic domain (391 amino acids) composed of a Ser/Pro-rich region followed by a Gly-rich region.
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PMID:Expression cloning of a novel scavenger receptor from human endothelial cells. 939 44

Oxidized LDL has been shown to exhibit a number of potentially proatherogenic actions and properties, including receptor-mediated uptake and lipid accumulation within macrophages. It has been postulated that rapid, unregulated uptake of oxidatively modified LDL could account for the transformation of monocyte-derived macrophages to foam cells in atherosclerotic lesions. In support of this hypothesis, oxidized LDL and lipid peroxidation products have been shown to exist in atheromas in vivo. Furthermore, a number of cell membrane proteins that can bind oxidized LDL with high affinity have been identified on the surface of macrophages, endothelial cells and smooth muscle cells. One characteristic that almost all of these 'scavenger receptors' share is the ability to bind with high affinity to a broad spectrum of structurally unrelated ligands. Of all of the different classes of scavenger receptors that have been identified, the scavenger receptor class A type I/II (SR-AI/II) has received the most attention. Studies with macrophages from mice deficient in the gene for SR-AI/II provide direct evidence that a receptor other than the SR-AI/II is responsible for most of the uptake of oxidized LDL in murine macrophages. This article provides an overview of the characterization and functions of the scavenger receptors that have been shown to interact with oxidized LDL, including SR-AI/II, CD36, SR-BI, macrosialin/CD68, LOX-1, and SREC. Isolation and characterization of these and other scavenger receptors has increased our understanding of their role in the uptake of oxidized LDL and the pathogenesis of atherosclerosis.
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PMID:Scavenger receptors and oxidized low density lipoproteins. 1051 Dec 92

Recent progress in the research of oxidized LDL has revealed that this lipoprotein causes not only foam cell transformation of macrophages but also several endothelial dysfunction, and the effects on endothelial cells are also involved with the process of atherogenesis. Receptors for oxidized LDL on endothelial cells, such as LOX-1 and SREC, have been cloned and their characteristics are now under investigation. In addition to lowering plasma cholesterol level, it is expected that new strategies to prevent atherosclerosis is established by focusing on the endothelial injury caused by oxidized LDL.
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PMID:[Endothelial injury by oxidized LDL]. 1063 93

Lectin-like oxidized LDL receptor (LOX)-1 is a type II membrane protein that belongs to the C-type lectin family of molecules, which can act as a cell-surface endocytosis receptor for atherogenic oxidized LDL. LOX-1 can support binding, internalization and proteolytic degradation of oxidized LDL, but not of significant amounts of acetylated LDL, which is a well-known high-affinity ligand for class A scavenger receptors and scavenger receptor expressed by endothelial cells (SR-EC). LOX-1 is initially 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 stimuli, such as tumour necrosis factor-alpha, transforming growth factor-beta and bacterial endotoxin, as well as angiotensin II, oxidized LDL itself and fluid shear stress. In addition, LOX-1 expression is detectable in cultured macrophages and activated vascular smooth muscle cells. In vivo, endothelial cells that cover early atherosclerotic lesions, and intimal macrophages and smooth muscle cells in advanced atherosclerotic plaques can express LOX-1. Cell-surface LOX-1 can be cleaved through some protease activities that are associated with the plasma membrane, and released into the culture media. Purification of soluble LOX-1 and the N-terminal amino-acid sequencing identified the two cleavage sites (Arg86-Ser87 and Lys89-Ser90), both of which are located in the membrane proximal extracellular domain of LOX-1. Measurement of soluble LOX-1 in vivo may provide a novel diagnostic tool for the evaluation and prediction of atherosclerosis and vascular disease.
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PMID:Roles of lectin-like oxidized LDL receptor-1 and its soluble forms in atherogenesis. 1150 27

Advanced glycation end products (AGEs) are nonenzymatically glycosylated proteins, which accumulate in vascular tissues in aging and diabetes. Receptors for AGEs include scavenger receptors, which recognize acetylated low density lipoproteins (Ac-LDL) such as scavenger receptor class AI/AII (SR-A), cell surface glycoprotein CD36, scavenger receptor class B type I (SR-BI), and lectin-like oxidized low density lipoprotein receptor-1. The broad ligand repertoire of these receptors as well as the diversity of the receptors for AGEs have prompted us to examine whether AGEs are also recognized by the novel scavenger receptors, which we have recently isolated from a cDNA library prepared from human umbilical vein endothelial cells, such as the scavenger receptor expressed by endothelial cells-I (SREC-I); the fasciclin EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1 (FEEL-1); and its paralogous protein, FEEL-2. At 4 degrees C, (125)I-AGE-bovine serum albumin (BSA) exhibited high affinity specific binding to Chinese hamster ovary (CHO) cells overexpressing FEEL-1 (CHO-FEEL-1) and FEEL-2 (CHO-FEEL-2) with K(d) of 2.55 and 1.68 microg/ml, respectively, but not to CHO cells expressing SREC (CHO-SREC) and parent CHO cells. At 37 degrees C, (125)I-AGE-BSA was taken up and degraded by CHO-FEEL-1 and CHO-FEEL-2 cells but not by CHO-SREC and parent CHO cells. Thus, the ability to bind Ac-LDL is not necessarily a prerequisite to bind AGEs. The (125)I-AGE-BSA binding to CHO-FEEL-1 and CHO-FEEL-2 cells was effectively inhibited by Ac-LDL and polyanionic SR-A inhibitors such as fucoidan, polyinosinic acids, and dextran sulfate but not by native LDL, oxidized LDL, or HDL. FEEL-1, which is expressed by the liver and vascular tissues, may recognize AGEs, thereby contributing to the development of diabetic vascular complications and atherosclerosis.
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PMID:FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. 1247 45

By inducing vascular inflammation, trimethylamine-N-oxide (TMAO) is associated with endothelial dysfunction, atherosclerosis, and enhanced risk of cardiovascular diseases in humans. However, the underlying mechanisms are unknown. Expression of several genes related to arteriosclerosis, inflammasomes, and endothelial dysfunction was quantified by polymerase chain reaction after exposure to TMAO. LOX-1, ICAM-1, and NLRP3 were also quantified by Western blot, whereas leukocytic adhesion was examined using fluorescently labeled U937 cells. Scavenger receptors, adhesion molecules, and other genes associated with atherosclerosis were induced in endothelial cells exposed to TMAO. On the other hand, apigenin, a flavonoid that is abundant in parsley and celery, prevents initial arteriosclerosis events in endothelial cells. Apigenin reversed the effects of TMAO on mRNA expression of LOX-1, SREC, SR-PSOX, NLRP3, ASC, TXNIP, VCAM-1, ICAM-1, and MCP-1, as well as protein expression of LOX-1, the adhesion molecule ICAM-1, and the inflammasome protein NLRP3. Apigenin also suppressed leukocyte adhesion and uptake of acetylated low-density lipoprotein. The data indicate that expression of scavenger receptors and adhesion molecules in response to TMAO, along with formation of NLRP3 inflammasomes, may drive endothelial dysfunction through uptake of acetylated low-density lipoprotein and lymphocyte adhesion. Apigenin reverses these effects, implying that it may also prevent arteriosclerosis.
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PMID:Dietary Apigenin Reduces Induction of LOX-1 and NLRP3 Expression, Leukocyte Adhesion, and Acetylated Low-Density Lipoprotein Uptake in Human Endothelial Cells Exposed to Trimethylamine-N-Oxide. 3151 78