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

The aim of the study is to identify the effects and underlying mechanisms of visfatin on inflammation and necroptosis in vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with visfatin or pretreated with Polyinosinic acid (LOX-1 inhibitor). By using the Western blot, RT-PCR, immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), MTT and flow cytometry technique, the occurrence of inflammation and necroptosis in HUVECs were evaluated. Our results showed that 100 ng/mL visfatin significantly increased the mRNA and protein expression of monocyte chemotactic protein 1 (MCP-1) and LOX-1 after 24 hours' treatment in HUVECs. However, pretreatment with Polyinosinic acid could significantly reduce the expression of MCP-1 compared with visfatin group. Additionally, 100 ng/mL visfatin could induce the production of necrotic features and increase the mRNA expression of BMF (one of the markers of necroptosis), while pretreating with Polyinosinic acid markedly downregulated the mRNA expression of BMF gene and promoted the cell proliferation. These results indicate that visfatin might induce inflammation and necroptosis via LOX-1 in HUVECs, suggesting that visfatin plays a central role in the development of atherosclerosis.
Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation/chemically induced* ; Necroptosis ; Nicotinamide Phosphoribosyltransferase ; Scavenger Receptors, Class E/genetics*

OBJECTIVETo explore the regulational effect of oxidized low-density lipoprotein (Ox-LDL) on expression of type A scavenger receptor (SR-A) in human mesangial cells (HMC).

METHODSHMC line (HMCL) with high expression of SR-A (HMCL-SRA) was established after stable transfection of expressive vector with cDNA encoding SR-A. Uptake of Ox-LDL by HMCL was evaluated using Oil Red "O" staining. SR-A mRNA expression was examined using reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSMore uptake of Ox-LDL was observed in the HMCL-SRA than that in the untransfected HMCL. Ox-LDL could induce SR-A mRNA expression in HMC in a dose-dependent manner, and reached a peak level after 24 h of stimulation. After 24 h of stimulation with Ox-LDL at the dose of 10, 50 and 100 micrograms/ml, SR-A mRNA expression was up-regulated to 1.35, 1.83 and 2.30-fold of controls, respectively. However, LDL had no effect on the expression of SR-A.

CONCLUSIONSIt suggests that SR-A be a major binding receptor to uptake Ox-LDL in HMC. Ox-LDL may promote the progression of chronic renal diseases through up-regulation of SR-A.

Cells, Cultured ; DNA, Complementary ; Glomerular Mesangium ; cytology ; metabolism ; Humans ; Lipoproteins, LDL ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Immunologic ; biosynthesis ; genetics ; Receptors, Scavenger ; Reverse Transcriptase Polymerase Chain Reaction ; Scavenger Receptors, Class A ; Transfection ; Up-Regulation

OBJECTIVE: To investigate the effect of miR-590-5p on the expression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) in apoptotic human umbilical vein endothelial cells (HUVECs) induced by ox-LDL, and to explore the role of miR-590-5p in modulating HUVECs apoptosis. METHODS: HUVECs were exposed to ox-LDL (50 μg/mL) for 0 to 48 h. Apoptosis was detected by Annexin V-FITC stain and was distinguished from necrosis by propidium iodide (PI) staining. The relative expression level of miR-590-5p in HUVECs was analyzed using real-time quantitative PCR (RT-qPCR). HUVECs were transfected with miR-590-5p mimics or miRNA mimics control followed by 50 μg/mL ox-LDL stimulation for 48 h. LOX-1 mRNA and protein were measured by RT-qPCR and Western blot, and apoptosis in HUVECs was analyzed by flow ctyometry after Annexin V-FITC/PI double stain. RESULTS: Incubation of HUVECs with 50 μg/mL ox-LDL for 0 to 48 h resulted in a time-dependent induction of apoptotic cell death and down-regulation of miR-590-5p. Transfection of miR-590-5p mimics suppressed LOX-1 expression at both mRNA and protein levels, leading to a reduction of ox-LDL-induced apoptosis in HUVECs. CONCLUSION MiR-590-5p protects endothelial cells from ox-LDL induced apoptosis by inhibiting the expression of LOX-1.
Apoptosis ; genetics ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Lipoproteins, LDL ; pharmacology ; MicroRNAs ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Scavenger Receptors, Class E ; genetics ; metabolism ; Transfection

OBJECTIVETo explore action mechanism of electroacupuncture for coronary atherosclerotic heart disease (CHD) in order to provide experimental support for clinical acupoint selection.

METHODSAmong sixty clean-grade healthy male Wistar rats, twenty-four cases were randomly selected as a normal control group and an electroacupuncture (EA) preconditioning group, 12 cases in each one. Then rats in the EA preconditioning group and the rest 36 rats were fed with high fat diet for 12 weeks to duplicate the CHD model. When the models were successfully established, the rats were randomly divided into a model control group, an EA group and a medication group, 12 cases in each one. EA was applied with Hwa-to SDZ-IV apparatus in the EA preconditioning group at "Neiguan" (PC 6) and "Xinshu" (BL 15), 1 mA in current intensity, 2 Hz in frequency, 30 min per times, once every other day for 14 weeks. When model was established, the same acupoint and method was used in the EA group for 2 weeks while intragastric administration of atorvastatin mixed suspension, 0.25 mg/kg, once a day, was applied in the medication group for 2 weeks. The content of oxidized low-density lipoprotein (oxLDL) in the serum was tested by double antibody enzyme-linked immunosorbent assay (ELISA) while content of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) in coronary arterial tissue was test by western blot method. Expression of LOX-1 mRNA was tested by fluorogenic quantitative polymerase chain reaction (PCR).

RESULTSAfter model was duplicated successfully, the content of oxLDL in the serum and the expression of LOX-1 and its mRNA in coronary arterial tissue in the model control group were increased significantly compared with those in the normal control group (all P < 0.01). Compared with the model control group, the content of oxLDL in the serum and the expression of LOX-1 and its mRNA in coronary arterial tissue in the EA preconditioning group, EA group and medication group were significantly reduced (all P < 0.01).

CONCLUSIONThe electroacupuncture at "Neiguan" (PC 6) and "Xinshu" (BL 15) could effectively reduce the content of oxLDL in the serum and expression of LOX-1 and its mRAN in coronary arterial tissue in CHD rats. The oxidative modificatory low-density lipoprotein and its specific receptor system could be one of the ways to prevention and treatment of acupuncture for CHD.

Animals ; Coronary Disease ; genetics ; metabolism ; therapy ; Disease Models, Animal ; Electroacupuncture ; Humans ; Lipoproteins, LDL ; genetics ; metabolism ; Male ; Rats ; Rats, Wistar ; Scavenger Receptors, Class E ; genetics ; metabolism

The present paper is to research the expression level of the mRNA of scavenger receptor class B type 1-receptor of high-density lipoprotein in endothelial cells after being treated by different shear stress. The second to fourth generations of the cultured human umbilical vein endothelial cells (HUVECs) were used in the experiment. The cells were divided into two groups. The first group was the control group which was not dealt with shear stress; the second group was the experimental group which concluded low shear stress group (4.2 dyne/cm2), moderate shear stress group (8.4 dyne/cm2) and high shear stress group (15 dyne/cm2). The load time was 1h, 2h, 4h and 8h, respectively. Harvesting the cells and extracting total RNA after being treated by different shear stresses, the expression level of the SR-B1 mRNA was detected by semi-quantitative RT-PCR technic. It was found that the expression of SR-B1 mRNA became weaker and weaker compared to the control group when it was stimulated continuously by the low shear stress, the lowest expression of SR-B1 mRNA appeared at 8h. In the moderate shear stress group, the expression of SR-B1 mRNA increased obviously. Compared to the control group, there was significant difference after being treated with 2h. In the high shear stress group, the expression of SR-B1 mRNA increased immediately when it was stimulated by the shear stress. And the expression of SR-B1 mRNA arrived peak value at 4h. Compared to the control group, there was significant difference after being treated for 1h. It was concluded that the harmful mechanism of the low shear stress is that it can increase the incidence of the atherosclerosis by reducing the reverse cholesterol transport and endothelial protection through decreasing the expression of the SR-B1. Otherwise, the high shear stress prevent the genesis of atherosclerosis by the contrary mechanism.
Atherosclerosis ; etiology ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Scavenger Receptors, Class B ; genetics ; metabolism ; Stress, Mechanical

Objective To explore the relationship between scavenger receptor class B member 1 (SCARB1) gene promoter methylation and the pathogenesis of coronary artery disease. Methods A total of 120 patients with coronary heart disease treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from December 2018 to May 2020 were selected as the case group,while 140 gender and age matched healthy participants were randomly selected as the control group for a case-control study.The methylation status was detected by high-throughput target sequencing after bisulfite converting,and the methylation of CpG sites in the promoter region of SCARB1 gene was compared between the two groups. Results The case group showed higher methylation level of SCARB1+67 and lower methylation level of SCARB1+134 than the control group (both P<0.001),and the differences remained statistically significant in men (both P<0.001) and women (both P<0.001).The overall methylation level in the case group was lower than that in the control group [(80.27±2.14)% vs.(81.11±1.27)%;P=0.006],while this trend was statistically significant only in men (P=0.002). Conclusion The methylation of SCARB1 gene promotor is associated with the pathogenesis and may participate in the occurrence and development of coronary heart disease.
Male ; Humans ; Female ; Methylation ; Case-Control Studies ; China ; Coronary Artery Disease/genetics* ; Promoter Regions, Genetic ; DNA Methylation ; Scavenger Receptors, Class B/genetics*

OBJECTIVETo assess the value of serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and LOX-1 mRNA expression in peripheral blood mononuclear cells in early diagnosis of acute coronary syndrome (ACS).

METHODSEnzyme-linked immunosorbent assay was used to detect the levels of plasma ox-LDL and LOX-1 in 95 patients with ACS, 60 with stable angina pectoris (SAP) and 40 normal control subjects. The expression of LOX-1 mRNA in peripheral blood mononuclear cells was detected by RT-PCR in the 3 groups.

RESULTSThe levels of ox-LDL, LOX-1 and LOX-1 mRNA in the peripheral blood mononuclear cells were significantly higher in ACS patients than in SAP patients and normal control subjects (P<0.05). In ACS group, the level of plasma ox-LDL was significantly correlated to serum LOX-1 and LOX-1 mRNA expression in peripheral mononuclear cells.

CONCLUSIONThe level of plasma soluble LOX-1 and LOX-1 mRNA in peripheral mononuclear cells are significantly increased in ACS, and when combined, they provide a useful means for detecting ACS in the prophase.

Acute Coronary Syndrome ; blood ; diagnosis ; Aged ; Early Diagnosis ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Scavenger Receptors, Class E ; blood

OBJECTIVETo establish a new drug screening model based on transcriptional regulation of human high density lipoprotein (HDL) receptor gene CD36 and LIMPII analogous-1 (CLA-1) for discovering up-regulator of this receptor.

METHODSThe upstream regulatory sequence of CLA-1 was obtained by polymerase chain reaction. A recombinant reporter plasmid pGL3-CLAP was constructed by inserting the regulatory sequence upstream of luciferase gene of pGL3-Basic. Human hepatoma cell line BEL-7402 was transfected with pGL3-CLAP. Samples were detected by testing luciferase activity of transfected BEL-7402 cells in microtiter wells.

RESULTSThe drug screening model was established and optimized. Significant difference was present between pGL3-CLAP and pGL3-Basic transfected BEL-7402 cells (P< 0.001), and coefficient of variation was less than 10%. After primary and secondary screening, 1 compounds and 3 fermentation extracts had up-regulating activities.

CONCLUSIONThis new drug screening model may be efficiently used to screen up-regulators of human HDL receptor expression, which might become lead compounds for new anti-atherosclerosis drugs.

CD36 Antigens ; Cholesterol Esters ; metabolism ; Drug Evaluation, Preclinical ; methods ; Gene Expression Regulation ; drug effects ; Humans ; Hypolipidemic Agents ; chemical synthesis ; pharmacology ; Lipoproteins, HDL ; genetics ; metabolism ; RNA, Messenger ; metabolism ; RNA-Binding Proteins ; Receptors, Immunologic ; genetics ; Receptors, Lipoprotein ; genetics ; Receptors, Scavenger ; Scavenger Receptors, Class B ; Transcription, Genetic ; drug effects ; Up-Regulation

The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT-GT), rs486907 (AG) and rs3747531 (CG-CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.
Aged ; Aged, 80 and over ; Cohort Studies ; Disease Progression ; Endoribonucleases/*genetics ; Gene Frequency ; Genetic Markers/genetics ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasm Proteins/*genetics ; *Polymorphism, Single Nucleotide ; Prognosis ; Prostate/metabolism/*pathology ; Prostatic Neoplasms/*diagnosis/*genetics ; Scavenger Receptors, Class A/*genetics