Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidized low-density lipoprotein (Ox-LDL) has been implicated in the attenuated endothelium-dependent vasodilatation in atherosclerotic arteries and, possibly, in hypertension. The aim of the present study was to investigate gene expression of recently-identified endothelial Ox-LDL receptor (LOX-1) in hypertensive state. SHR-SP, WKY, Dahl salt-sensitive (DS) and salt-resistant rats (DR) were fed salt-loaded or control diet. RNA was extracted from the aorta and vein. LOX-1 expression was examined by Northern blotting. LOX-1 mRNA was low in the aorta and vein of WKY, whereas it was markedly upregulated in those of SHR-SP. LOX-1 expression was low in the aorta of DR on both diets and of DS on a control diet, whereas it was elevated in that of salt-loaded DS. These results indicated that LOX-1 expression in the aorta and vein was upregulated in hypertensive rats, which may be involved in the impaired endothelium-dependent vasodilation in these rats.
 ...
PMID:Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats. 929 91

We report the identification of a unique repetitive sequence in the rat endothelial receptor for oxidized low-density lipoprotein (LOX-1) and unexpected blood-pressure-associated regulation of its expression, a new link between lipid metabolism and blood-pressure control. A rat aorta cDNA library was constructed and screened with a probe synthesized by degenerate PCR. Rat LOX-1 cDNA encoded a protein of 364 amino acids that showed approximately 60% similarity to its bovine and human counterparts. The protein consisted of intracellular N-terminal, transmembrane and extracellular lectin-like domains. Rat LOX-1 was unique in having three repeats of a 46-amino-acid motif between the transmembrane and lectin-like regions. Two isoforms of mRNA were found to be generated by alternative use of two polyadenylation signals in a tissue-specific manner. The 3'-untranslated region contained multiple A+U-rich elements for rapid degradation of mRNA. Northern-blot analysis revealed that LOX-1 mRNA was expressed predominantly in the lung. Quite unexpectedly, the expression was dramatically up-regulated in the aorta in hypertensive SHR-SP/Izm rats compared with very low levels in control WKY/Izm rats, suggesting a potential role for LOX-1 in the pathogenesis of hypertension as well as atherosclerosis.
 ...
PMID:Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1). 949 15

Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-beta 1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
 ...
PMID:Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis. 1100 13

Current gene delivery vectors demonstrate inefficient and nonselective gene transfer to vascular endothelial cells, limiting their use in cardiovascular gene transfer and therapy. The lectinlike oxidized LDL receptor (LOX-1) is expressed selectively at low levels on endothelial cells but is strongly upregulated in dysfunctional endothelial cells associated with hypertension and atherogenesis. Using LOX-1 as a target receptor, we have sought to isolate peptide ligands that mediate binding to the extracellular domain of LOX-1 as a definitive step in the development of targeted gene transfer aimed at dysfunctional endothelium. To achieve this, we ectopically overexpressed LOX-1 in cells lacking endogenous LOX-1 by using an episomally maintained expression system and designed a novel subtractive phage display strategy to identify peptides selective for LOX-1. After extensive biopanning, we sequenced individual phage and identified 60 novel peptides. This population of peptides contained a number of potential consensus motifs. To define the selectivity of individual peptides for LOX-1 with the use of an independent gene transfer system, we developed a novel adenoviral vector to overexpress LOX-1 transiently in primary cells and cell lines. We then quantified recovery of each peptide from LOX-1-positive and LOX-1-negative cells after adenovirus-mediated gene transfer. This strategy confirmed selectivity to LOX-1 for many peptides and highlighted the peptides LSIPPKA, FQTPPQL, and LTPATAI as principal candidates. These peptides will be useful for the selective targeting of viral and nonviral gene transfer vectors to endothelial cells expressing the LOX-1 receptor in vitro and in vivo and in particular dysfunctional endothelial cells associated with hypertension and atherosclerosis.
Hypertension 2001 Feb
PMID:Identification of peptides that target the endothelial cell-specific LOX-1 receptor. 1123 Mar 17

Oxidative stress has been implicated in atherosclerosis and its underlying conditions. LOX-1 is a novel endothelial receptor for oxidized low-density lipoprotein which might mediate endothelial dysfunction and subsequent atherogenesis. In the present study, we examined LOX-1 gene regulation by oxidative stress. First, superoxide anions generated by hypoxanthine and xanthine oxidase as well as hydrogen peroxide increased LOX-1 mRNA expression in cultured aortic endothelial cells. Homocysteine, an atherogenic substance believed to exert its effects through oxidative stress, enhanced endothelial LOX-1 gene expression, which was suppressed by N-acetylcysteine. Second, rats receiving angiotensin II for 10 days manifested hypertension and LOX-1 upregulation in aortic endothelium via AT1 receptor. Tempo, a superoxide dismutase mimetic, alleviated LOX-1 augmentation induced by angiotensin II. These results indicated redox-sensitive upregulation of LOX-1 mRNA in both in vitro and in vivo systems, suggesting its potential role in atherosclerosis.
 ...
PMID:Redox-sensitive regulation of lox-1 gene expression in vascular endothelium. 1123 17

Recent progress in the study of atherosclerosis revealed that the proatherogenic property of LDL is attributable to oxidized LDL. Macrophages recruited to vascular wall phagocytose oxidized LDL and transformed into foam cells, which is a hallmark of atheroma. Endothelial cells also binds oxidized LDL and changes its phenotype to the status of "endothelial dysfunction." We successfully cloned the endothelial receptor for oxidized LDL, designated LOX-1. LOX-1-mediated action of oxidized LDL induces the decrease in NO release and the increased expression of adhesion molecules, which are typical changes in endothelial dysfunction. The expression of LOX-1 is quite inducible. Proinflammatory cytokines, etc. induce the expression of LOX-1 in vitro; and proatherogenic conditions, e.g., hypertension, hyperlipidemia, and diabetes, induce the expression of LOX-1 in vivo. This manner of expression suggests the importance of LOX-1 in pathological settings. LOX-1 binds not only oxidized LDL, but also binds apoptotic cells and activated platelets through the interaction with anionic phospholipids. This property might bridge atherosclerosis and thrombosis. A novel system to detect LOX-1 ligand in plasma detected the increased level of LOX-1 ligand in hypercholesterolemic rabbits compared with normal ones. This system might be useful to predict the status of endothelial function and the risk of ischemic heart disease.
 ...
PMID:[Molecular identification of LOX-1 and analysis of its pathophysiological role]. 1191 16

Oxidatively modified low-density lipoprotein (ox-LDL) leads to endothelial activation, dysfunction and injury. Recently, a novel lectin-like receptor for ox-LDL (LOX-1) has been identified, primarily in the endothelial cells, and it allows uptake of ox-LDL into endothelial cells. This receptor is transcriptionally upregulated by tumor necrosis factor-alpha, angiotensin II, shear stress and ox-LDL itself. The expression of this receptor activates a variety of intracellular processes that lead to expression of adhesion molecules and endothelial activation. This receptor is highly expressed in the blood vessels of animals and humans with hypertension, diabetes mellitus and atherosclerosis. Expression of this receptor may also be relevant in intra-arterial thrombogenesis and myocardial ischemia-reperfusion injury. Identification and regulation of this receptor and understanding of signal transduction pathways may lead to new therapies of diseases characterized by endothelial dysfunction.
 ...
PMID:Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor. 1198 3

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was initially identified as the major receptor for oxidized LDL (OxLDL) in endothelial cells. Its inducible expression in macrophages and smooth muscle cell was also observed. LOX-1 is a Type II membrane protein with a typical C-type lectin structure at the extracellular C-terminus. It can be cleaved by an unknown protease at the extracellular juxtamembrane region to release the soluble form of LOX-1. The extracellular domains of LOX-1 are post-translationally modified by N-linked glycosylation. Mutagenesis studies revealed that the lectin domain of LOX-1 is the functional domain that recognizes the LOX-1 ligand. The C-terminal end residues and several conserved positively charged residues spanning the lectin domain are essential for OxLDL binding. LOX-1 activation by OxLDL causes endothelial changes that are characterized by activation of nuclear factor-kappaB through an increased reactive oxygen species, subsequent induction of adhesion molecules, and endothelial apoptosis. In vitro, expression of LOX-1 is induced by many inflammatory cytokines, oxidative stress, hemodynamic stimuli, and OxLDL. In vivo, the expression is enhanced in pro-atherogenic settings including, hypertension, hyperlipidemia, and diabetes, and, indeed, is accumulated in the atherosclerotic and glomerulosclerotic lesions. LOX-1 binds multiple classes of ligands that are implicated in the pathogenesis of atherosclerosis. Besides OxLDL, LOX-1 can recognize apoptotic/aged cells, activated platelets, and bacteria, implying versatile physiological functions. Taken together, all these findings support the possible contribution of LOX-1 to the pathogenesis of vascular disorders, particularly atherosclerosis. Development of antagonists for LOX-1 might be a good therapeutic approach to vascular diseases.
 ...
PMID:LOX-1, the receptor for oxidized low-density lipoprotein identified from endothelial cells: implications in endothelial dysfunction and atherosclerosis. 1216 30

There is strong evidence for the role of oxidative stress in all stages of atherosclerosis. Oxidized low density lipoprotein (ox-LDL), a marker of oxidative stress, is present in the plasma as well as in the atherosclerotic arteries of patients with atherosclerosis. Ox-LDL leads to endothelial activation, dysfunction and injury. Recently, a novel lectin-like receptor for ox-LDL (LOX-1) has been identified, primarily in the endothelial cells, that allows uptake of ox-LDL into endothelial cells. This receptor is transcriptionally upregulated by tumour necrosis factor-a, angiotensin II, shear stress and ox-LDL. The expression of this receptor activates a variety of intracellular processes that leads to expression of adhesion molecules and endothelial activation. Recent studies show that LOX-1 activation leads to the expression of CD40/40 L in endothelial cells and upregulation of matrix metalloproteinases. This receptor is highly expressed in blood vessels of animals and humans with hypertension, diabetes mellitus and atherosclerosis. Co-localization of LOX-1 along with ox-LDL in the rupture-prone plaque suggests that this receptor may be involved in the precipitation of acute myocardial ischemia. Identification and regulation of this receptor and understanding of signal transduction pathways may lead to new therapies in disease states characterized by endothelial dysfunction.
 ...
PMID:The role of LOX-1, a novel lectin-like receptor for oxidized low density lipoprotein, in atherosclerosis. 1530 3

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) are molecules involving in the initiation and progression of atherosclerosis. In order to examine a possible difference in LOX-1 and MCP-1 expressions depending on the severity of early stage of atherosclerosis, we investigated atherosclerotic changes by exposure to hypertension and hyperlipidemia in common carotid arteries (CCAs) of stroke-prone spontaneously hypertensive rat (SHR-SP). Three rat model groups such as control [Wistar Kyoto rat (WKY) group], hypertension (SHR-SP group) and hypertension + hyperlipidemia [SHR-SP + high fat and cholesterol (HFC) group] were used. Body weights, brain weights, systolic blood pressures and serum levels of total cholesterol, low-density lipoprotein and triglyceride were measured at 0, 5, 10 and 15 days after appropriate diet. Immunohistochemistry showed that the positive area and the strength of LOX-1 and MCP-1 were larger in the SHR-SP + HFC group than in the SHR-SP group, while no immunoreactivities were found in the WKY group. Conventional RT-PCR and real-time PCR analyses showed that mRNAs of those in the SHR-SP group were higher with greater up-regulation in the SHR-SP + HFC group. LOX-1 and MCP-1 expressions were coordinately up-regulated at mRNA and protein levels in an early stage of sclerosis depending on the severity of atherosclerotic stress. Activations of LOX-1 and MCP-1 are collectively involved in the early stage of atherosclerosis.
 ...
PMID:Severity dependent up-regulations of LOX-1 and MCP-1 in early sclerotic changes of common carotid arteries in spontaneously hypertensive rats. 1549 20


1 2 3 4 Next >>