Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.
Humans ; Atherosclerosis ; Scavenger Receptors, Class E/physiology* ; Biomarkers ; Plant Extracts ; Lipoproteins, LDL

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

OBJECTIVETo investigate whether oxidized low-density lipoprotein (oxLDL) affects the survival and activity of endothelial progenitor cell (EPC) and whether the effects are mediated by lectin-like oxidized low-density lipoprotein receptor (LOX-1).

METHODSCD34+ cells isolated from human umbilical blood were cultured in endothelial cell growth medium-2 (EGM-2). After 14 days of culture, some EPCs were stimulated with 10, 25, 50 microg/ml of oxLDL for 48 hours; some were preincubated with LOX-1 mAb, a blocking antibody of LOX-1, for 24 hours, then exposed to 50 microg/ml oxLDL for 48 hours; others without any further treatment were used as control. The survival of EPC and the ability of adhesion, migration, and tube formation were examined. The levels of LOX-1 protein and mRNA expression were also assayed.

RESULTSIncubation with oxLDL at concentrations of 25 microg/ml or higher resulted in a dose-dependent increase of EPC apoptosis [25 microg/ml: (15.8 +/- 1.1.0%, 50 microg/ml: (18.8 +/- 2.0)% versus control: (9.0 +/- 1.2)%; P < 0.05]. Treated with oxLDL led to a significantly reduced migratry rate [25 microg/ml: (5.7 +/- 1.0)%, 50 microg/ml: (5.1 +/- 0.8)% versus control: (9.5 +/- 0.8)%; P < 0.05]. EPC treated with oxLDL showed a dose-dependent reduction of adhesion to fibronectin (25 Kg/ml: 33 +/- 2, 50 microg/ml: 30 +/- 3 versus control: 37 +/- 5; P < 0.05). Treatment with oxLDL impaired the in vitro vasculogenesis ability of EPCs. The total length of the tube structures in each photograph was decreased [25 microg/ml: (2.9 +/- 0.5) mm, 50 microg/ml: (1.8 +/- 0.5) mm versus control: (5.0 +/- 0.6) mm; P < 0.05]. The tube structure was severely disrupted, resulting in an incomplete and sparse tube network. However, all the detrimental effects on EPC were attenuated by pretreatment of EPC with LOX-1 mAb. In addition, Western blot analysis revealed that oxLDL increased LOX-1 protein expression from 100% to (172 +/- 8)% at a dose of 50 microg/ml. Furthermore, oxLDL caused an increase in LOX-1 mRNA expression from 100% to (174 +/- 39)% at a dose of 50 microig/ml.

CONCLUSIONOxLDL can directly inhibit EPC survival and activity and these effects are mediated by its receptor, LOX-1.

Antigens, CD34 ; metabolism ; Apoptosis ; Cell Adhesion ; Cell Movement ; Cell Survival ; Cells, Cultured ; Endothelial Cells ; drug effects ; physiology ; Fetal Blood ; cytology ; Humans ; Lipoproteins, LDL ; pharmacology ; physiology ; Neovascularization, Physiologic ; Scavenger Receptors, Class E ; biosynthesis ; physiology ; Stem Cells ; drug effects ; physiology

OBJECTIVERecent studies have shown that Toll-like receptor 4 (TLR4), a mediator of for innate immune responses, is involved in the initiation and progression of atherosclerosis. TLR4 activation mediates the expression of chemokines and cytokines through activation of NF-kappaB. We investigated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (CAM-1), E-selectin induced by TLR4/NF-kappaB in human umbilical vein endothelial cells (HUVECs), and their effects on adhesion of monocyte to HUVECs.

METHODSHUVECs were incubated with purified LPS for 24 h. TLR4, LOX-1, ICAM-1, E-selectin mRNA were measured by RT-PCR; the protein expression of TLR4, LOX-1 and activation of NF-kappaB were detected by Western blot; the adhesive percentage between HUVECs and monocytes was determined by direct counting.

RESULTSLPS (1 mg/L) not only enhanced expression of TLR4, activation of NF-kappaB and induction of LOX-1, ICAM-1, E-selectin expression, but also increased the percentage of monocyte adhesion to endothelium. Pretreatment of HUVECs with anti-LOX1, anti-ICAM-1 or anti E-selectin antibodies partly abolished the increase in monocyte adhesion to endothelium. NF-kappaB inhibitor CAPE suppressed LPS-induced these effects.

CONCLUSIONTLR4/NF-kappaB plays an important role in monocyte-endothelium adhesion partly through upregulation of LOX-1, ICAM-1 and E-selection expression, which may provide a target for the treatment of atherosclerosis.

Cell Adhesion ; Cells, Cultured ; E-Selectin ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Monocytes ; metabolism ; physiology ; NF-kappa B ; metabolism ; Scavenger Receptors, Class E ; metabolism ; Toll-Like Receptor 4 ; metabolism ; Umbilical Veins ; cytology

Atopic dermatitis (AD) is an inflammatory skin disorder that is both uncomfortable and distressing to patients, and its prevalence has been steadily increasing. It is obvious that the identification of efficient markers of AD in plasma would offer the possibility of effective diagnosis, prevention, and treatment strategies. In this study, a proteomic approach was used to analyze plasma glycoproteins from both children with AD and healthy child donors. Several protein spots showing significant quantitative changes in the AD patients were identified. Through sequential studies, it was confirmed that CD5L and ApoE were significantly up-regulated or down-regulated, respectively, in the plasma from AD patients compared with that from healthy donors. In addition, we suggest that the up-regulated CD5L in AD patients causes eosinophilia by inhibiting apoptosis or promoting the proliferation of eosinophils either in combination with or without IL-5. The glycoproteomic data in this study provides clues to understanding the mechanism of atopic alterations in plasma and suggests AD-related proteins can be used as candidate markers for AD.
Apolipoproteins E/*blood ; Biological Markers/blood ; Cell Line ; Cell Proliferation ; Child ; Dermatitis, Atopic/*metabolism ; Eosinophilia/metabolism ; Eosinophils/physiology ; Female ; Glycoproteins/*blood ; Humans ; Interleukin-5/metabolism ; Male ; Proteomics ; Scavenger Receptors, Class B/*blood

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