Effect of Ginkgo biloba Tablet on the Expression of Scavenger Receptor A of the Aortic Wall in Atherosclerotic Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the expression of Ginkgo biloba Tablet (GbT) on scavenger receptor A (SRA) of the aortic wall and changes of serum inflammatory factors in atherosclerotic rats, and to explore its new mechanism for fighting against atherosclerosis (AS).</p><p><b>METHODS</b>Totally 45 male Wistar rats were randomly divided into the control group, the model group, the GbT group, 15 rats in each group. Levels of blood glucose, blood lipids, blood calcium, serum C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (slCAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured in all rats. The expression of SRA in the aortic wall of atherosclerotic rats was observed by immunohistochemical assay. The correlation between the expression of SRA and levels of in-flammatory factors was also observed.</p><p><b>RESULTS</b>Compared with the control group, blood glucose and blood calcium obviously increased (P < 0.05); levels of TG, TC, and LDL-C were significantly elevated (P < 0.01); neointimal areas were significantly thickened, increased intima percentage was significantly enlarged, narrowed lumen index was significantly reduced; levels of CRP, sICAM-1, and sVCAM-1 were significantly elevated in the model group (all P < 0.01). Compared with the model group, blood glucose and blood calcium obviously decreased (P < 0.05); levels of TG, TC, and LDL-C significantly decreased (P < 0.01) in the GbT group. Aortic lumens were obviously narrower in the model group than in the GbT group (P < 0.05). SRA expressed at the aortic wall. The aforesaid 3 indices were significantly improved in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were significantly decreased in the GbT group than in the model group (P < 0.01). Serum levels of CRP, sICAM-1, and sVCAM-1 were positively correlated with the percentage of SRA positive expression area (r = 0.701, 0.604, 0.581, all P < 0.01).</p><p><b>CONCLUSIONS</b>Serum levels of inflammatory factors in atherosclerotic rats were elevated, and the expression of SRA in the aortic wall was enhanced. The expression of SRA was closely correlated with serum levels of inflammatory factors. GbT could decrease serum levels of inflammatory factors and inhibit the expression of SRA.</p>

Prognostic role of genetic biomarkers in clinical progression of prostate cancer

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.

Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages / 生理学报

The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 μmol/L thapsigagin (TG) for 4 h. In addition, RAW264.7 cells were incubated with 0.5, 1 and 2 mg/L TM for 4 h or treated with 2 mg/L TM for 1, 2 and 4 h, respectively. The intracellular total cholesterol (TC) content was measured using a tissue/cell total cholesterol assay kit. The protein and mRNA expressions of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot and real-time PCR, respectively. Dil-ox-LDL uptake was detected using a microplate reader. The results showed that ox-LDL-induced cholesterol accumulation in macrophages was attenuated by PBA, an ERS inhibitor. Ox-LDL caused significant SR-A1 upregulation with concomitant activation of ERS as assessed by upregulation of GRP78, whereas PBA significantly inhibited the ox-LDL-induced SR-A1 upregulation (P < 0.05) and slightly decreased GRP78 expression by 39.3% (P = 0.057). TM, an ERS inducer, upregulated SR-A1 protein expression and ox-LDL uptake in dose- and time-dependent manner, but had no significant effect on SR-A1 mRNA level. However, the TM- or TG-induced SR-A1 upregulation and ox-LDL uptake were significantly mitigated by PBA. These data indicate that ERS plays a critical role in ox-LDL-induced SR-A1 upregulation, which in turn enhances the foam cell formation by uptaking more ox-LDL.

Thymic stromal lmphopoietin pomotes macrophage-derived foam cell formation / 华中科技大学学报（医学）（英德文版）

The effect of thymic stromal lymphopoietin (TSLP) on macrophage-derived foam cell formation and the underlying mechanism were studied. Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein (ox-LDL). The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination. The expression levels of foam cell scavenger receptors (CD36 and SRA) as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting. As compared with the control group, TSLP treatment significantly promoted lipid accumulation in macrophages, significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner, and significantly reduced the expression of ABCA1 protein in a dose-dependent manner. No significant differences were noted between the TSLPR-antibody group and the control group. TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway, thereby promoting macrophage-derived foam cell formation.

Mechanisms of foam cell formation in smooth muscle cell derived from bone marrow stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a model of smooth muscle cells differentiated from bone mesenchymal stem cells (BMSC-SMCs) in vitro and explore the relationship between scavenger receptors A (SR-A) and caveolin-1.</p><p><b>METHODS</b>BMSCs were isolated from the femoral bone of SD rats by adherent culture. After treatment of the BMSC-SMCs with 80 mg/L ox-LDL for 72 h, Western blotting was performed to detect the expression of scavenger receptor SR-A, cell cholesterol transport protein ATP-binding cassette transporter Al (ABCA1) and caveolin-1.</p><p><b>RESULTS</b>BMCS-SMCs became foam cells after treatment with ox-LDL. BMSC-SMC gave rise to more foam cell formation than VSMCs did. Western blotting showed that treatment with 80 mg/L ox-LDL for 72 h resulted in significantly increased expression of SR-A and significantly decreased expressions of ABCA1 and caveolin-1.</p><p><b>CONCLUSIONS</b>Treatment of BMCS-SMCs with ox-LDL results in cholesterol ester accumulation in the cells to result in foam cells, the mechanism of which involves up-regulation of scavenger receptor SR-A expression and down-regulation of the reverse cholesterol transport protein ABCA1 and caveolin-1 expression.</p>

Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells.</p><p><b>METHODS</b>THP-1 cells were induced to differentiate into macrophages by PMA and treated with 0.1% BSA (control), ox-LDL (100 mg/L) or ox-LDL plus atorvastatin (5, 10, 20 micromol/L) for 24 hours. MCP-1 concentration in cell substratum was measured by ELISA. Scavenger receptor A expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL. The relationship between concentration of MCP-1 and the activity of scavenger receptor A was also analyzed.</p><p><b>RESULTS</b>Compared to the control cells, MCP-1 concentration in ox-LDL treated cells was significantly increased after 6 hours, peaked at 12 hours and was still significantly increased after 24 hours (all P < 0.05 vs. baseline). The activity of scavenger receptor A was also significantly increased in ox-LDL treated cells (P < 0.01 vs. control). The activity of scavenger receptor A proteins correlated positively to the concentration of MCP-1 in ox-LDL treated cells (r = 0.683, P < 0.01). Atorvastatin significantly attenuated these changes in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Scavenger receptor A and MCP-1 expressions were significantly increased in the course of monocyte lines THP-1 differentiating into macrophages and foam cells. The anti-atherosclerosis effect of atorvastatin might be partly achieved by inhibiting the secretion of MCP-1 and expression of scavenger receptor A in foam cells.</p>

Effects of oxidized low-density lipoprotein on expression of type A scavenger receptor in human mesangial cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>HMC 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).</p><p><b>RESULTS</b>More 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.</p><p><b>CONCLUSIONS</b>It 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.</p>

Scavenger receptors and atherosclerosis

Scavenger receptors were discovered as cell surface proteins capable of binding and internalization of modified lipoproteins. These receptors exhibit a broad ligand binding specificity including potential physiological and pathophysiological ligands other than modified lipoproteins. Different classes of scavenger receptors have been identified, and their relevance in normal and pathological conditions is under investigation. Recent in vitro and in vivo studies strongly support the role of class A and class B scavenger receptors in lipid transport and atherogenesis.