Abstract:CD147 is a member of the immunoglobulin super family, which can be highly expressed in inflammatory tissues and has a pro-inflammatory effect. Atherosclerosis is well known as a chronic inflammatory disease, and the mechanism of high expression of CD147 promoting atherosclerosis has been confirmed by a large number of studies. Understanding how CD147 promotes the occurrence and development of atherosclerosis can provide new ideas for the prevention and treatment of this disease. At the same time, a large number of compounds have been proved to be able to downregulate CD147 to have anti-atherosclerosis effect, which also provides a direction for drug design targeting CD147 in the future. This article reviews the mechanism of atherosclerosis induced by CD147 and the research progress of compounds that downregulate CD147.

Abstract:Aim To investigate the value of serum CD147 level in evaluating the prognosis of non-infarction related artery (non-IRA) after percutaneous coronary intervention (PCI). Methods 103 patients with ST-segment elevation myocardial infarction (STEMI) complicated with multi-vessel disease admitted to our hospital from March 2017 to March 2019 were selected. All patients were treated with non-IRA PCI 3~7 days after PCI successfully opened IRA. According to whether major adverse cardiovascular event (MACE) occurred 6 months after operation, the patients were divided into two groups:non-MACE group (n＝75) and MACE group (n＝28). According to Killip cardiac function classification standard, the patients were graded. Echocardiography and left ventricular ejection fraction (LVEF) were recorded. Coronary angiography was performed by Judkins method and the stenosis was recorded. The differences of general information and serum biochemical indexes were compared between the two groups. ROC curve was drawn to evaluate the diagnostic value of serum CD147 level for MACE after multi-vessel PCI in STEMI patients. COX regression model was used to analyze the risk factors of MACE after multi-vessel PCI in STEMI patients. Results Compared with non-MACE group, the proportion of hyperlipidemia, Killip Ⅱ~Ⅲ ratio, low density lipoprotein cholesterol and CD147 levels were higher in MACE group (P＜0.05), and LVEF was lower (P＜0.05). ROC results showed that the area under curve of serum CD147 in diagnosing MACE after multi-vessel PCI in STEMI patients was 0.834, the cut-off value was 625.58 ng/L, the corresponding sensitivity and specificity were 78.60% and 81.30% respectively, and the Youden index was 0.599. COX regression model showed that Killip Ⅱ~Ⅲ, LVEF＜45% and high level CD147 were independent risk factors for MACE after multi-vessel PCI in STEMI patients (P＜0.05). Conclusions CD147 is closely related to the prognosis of STEMI patients undergoing multi-vessel PCI. It has a certain diagnostic value for MACE after PCI in STEMI patients, and can provide a reference for the prognosis evaluation of STEMI patients undergoing multi-vessel PCI.

Abstract:Aim To investigate the influence of homocysteine (Hcy) on CD147 expression in human U-937 macrophages and intervention effect of rosuvastatin. Methods Human U-937 macrophages induced by PMA were treated with 0,0, 100 and 500 μmol/L Hcy for 48 hours respectively, CD147 expression was then analyzed using Western blot and RT-PCR. Different concentrations of rosuvastatin (10-8~10-5 mol/L) were added when U-937 macrophages were treated with 500 μmol/L Hcy. CD147 expression was then examined after incubating for 48 h. Cellular immumofluorescence method was used to detect the expression of CD147. Results Hcy significantly increased the expression of CD147 in a dose-dependent manner. Rosuvastatin (10-7~10-5 mol/L) significantly reversed the expression of Hcy-induced CD147 in U-937 macrophages in a dose-dependent manner. Cellular immumofluorescence demonstrated that the CD147 expression of U-937 macrophages was significantly increased by Hcy compared with control group, rosuvastatin (10-5 mol/L) cloud reverse the effect. Conclusion Hcy (100~500 μmol/L) significantly increased the production of CD147 in PMA-induced U-937 macrophages in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the expression of CD147 in PMA-induced U-937 macrophages induced by Hcy.

Abstract:Aim To investigate the effects and mechanisms of cyclophilin A (CypA) on the expression of ATP binding cassette trasporter A1 (ABCA1) and cholesterol efflux in THP-1 derived macrophages. Methods THP-1 cells were incubated with 160 nmol/L phorbol ester to transform into macrophages. THP-1 derived macrophages were exposed to 50 mg/L oxidized low density lipoprotein (ox-LDL) and cultured with typical approaches. Liquid scintillation counter was used to determine the efficiency of cholesterol efflux. Lipids contents were tested with high performance liquid chromatogram (HPLC). Real-time PCR and Western blot were used to quantify the expression of ABCA1 and nuclear factor-κB (NF-κB) nuclear translocation. Parthenolide was used as the specific inhibitor of NF-κB. CD147 was silenced with siRNA. Results CypA significantly reduced cholesterol efflux, promoted NF-κB nuclear translocation and downregulated ABCA1 expression. NF-κB inhibitor parthenolide interfered CypA-prevented ABCA1 expression and cholesterol efflux. After CD147 were silenced with siRNA, CypA inhibited NF-κB nuclear translocation, upregulated ABCA1 expression and promoted cholesterol efflux. Conclusion CypA prevented THP-1 derived macrophages cholesterol efflux by activing NF-κB in a CD147 dependent manner and downregulating ABCA1 expression.

Abstract:Aim To evaluate the effect of Alisol A 24-acetate on the protein expression of lipid metabolism factors ATP-binding cassette transporter A1 (ABCA1), class B scavenger receptor (CD36) and inflammatory factors extracellular matrix metalloproteinase inducer (CD147), matrix metalloproteinase-9 (MMP-9) in oxidized low density liprotein (ox-LDL)-stimulated rat peritoneal macrophages. Methods Rat peritoneal macrophages were respectively treated with 50 mg/L ox-LDL and 10 mg/L Dil-ox-LDL, and intervened with 10 mg/L Alisol A 24-acetate. Dil-ox-LDL accumulation in macrophages was observed with fluorescence microscope. The protein expression of ABCA1, CD147, CD36 and MMP-9 were detected by Western blot. Results After induced with 10 mg/L Dil-ox-LDL, a large number of Dil-ox-LDL accumulation was observed in peritoneal macrophages of rats. Intracellular Dil-ox-LDL accumulation was significantly reduced after 10 mg/L Alisol A 24-acetate intervention. Compared with the control group, the protein expressions of ABCA1, CD36 and CD147, MMP-9 were significantly increased in peritoneal macrophages after induced with 50 ox-LDL mg/L. After 10 mg/L Alisol A 24-acetate intervention, the protein expression of ABCA1 was increased further (P<0.01), and protein expressions of CD36, CD147 and MMP-9 were significantly inhibited (P<0.05 or P<0.01). Conclusions Alisol A 24-acetate can increase the expression of lipid metabolic factor ABCA1, inhibit the expression of CD36, and reduce cholesterol accumulation in macrophages. Also it can inhibit the secretion of inflammatory factors CD147 and MMP-9.

Abstract:Aim To investigate the effect on the expression of CD147 in acute myocardial infarction (AMI) patients as microRNA-548z (miR-548z) binding to the single nucleotide polymorphism (SNP) sites rs8259 T / A at CD147 gene 3′untranslated region (UTR). Methods Samples for the study were from 30 patients with AMI and 13 healthy people. Genotype of rs8259 sites on CD147 gene was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Quantitative polymerase chain reaction (qPCR) was used to detect the relative expression levels of miR-548z and CD147 mRNA in peripheral blood mononuclear cells (PBMC). The expression of CD147 protein in PBMCs was detected by Western Blot. The interaction between miR-548z and rs8259 different alleles was proved by luciferase reporter gene assay. Results The expression of miR-548z in AA and TT AMI patients, as well as in normal people appeared no significant difference (P>0.05). There was no significant difference between AA and TT patients with AMI in the expression levels of CD147 mRNA in PBMCs (P>0.05). The level of CD147 protein in AMI patients with AA genotype was significantly higher than the TT genotype group. The luciferase reporter gene assay showed that mimic miR-548z could does-dependly reduce the relative luciferase activity of constructs carrying the T allele. Conclusion MiR-548z could bind to rs8259 bearing T alleles on the 3′UTR of CD147 gene and negatively regulate the expression of CD147 protein in AMI patients.

Abstract:Aim To explore the expressions of cyclophilin A （CyPA）/CD147 in rabbit atherosclerotic vulnerable plaques.Methods 16 healthy male New Zealand rabbits （3 months） were randomly divided into control group and model group,8 rabbits in each group. Rabbit model with typical atherosclerotic vulnerable plaque was developed by injuring carotid intima with liquid nitrogen combined with high-fat diet. Meanwhile,the control group was fed with standard diet,and without injuriy. Expressions of C-reactive protein （CRP）,CyPA and CD147 in serum of rabbits were tested at the beginning and the 13th week. All rabbits were sacrificed after 13 weeks. Then paraffin-embedded sections were used for HE staining and Masson trichrome staining to analyze the changes of vascular morphology. Additionally,macrophagocyte,CyPA and CD147 monoclonal antibodies were applied for immunohistochemistry staining.Results Atherosclerotic vulnerable plaques were found in model group but not in control group. There were rich expressions of CyPA and CD147 with zonal distribution and co-location in the same atherosclerotic vulnerable plaques. The expressions of CyPA,CD147 and CRP in serum increased significantly in model group compared with those in control group at the 13th week （P<0.05）.Conclusions High expressions of CyPA and CD147 were found in atherosclerotic vulnerable plaques,and the expressions of CyPA and CD147 were the risk factors of the atherosclerotic vulnerable plaques,which have a positive correlation with the existence of atherosclerotic vulnerable plaques.

Abstract:Aim To analyze the polymorphism of the CD147 gene 3′UTR rs8259 in patients with ST-segment elevation myocardial infarction （STEMI）, and to study the relation between plasma levels, genotype of CD147 and STEMI.Methods The polymorphism of CD147 was detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and DNA sequencing method in 162 STEMI patients and 328 healthy persons. The plasma level of CD147 was determined by enzyme-linked immunosorbent assay （ELISA）. Results STEMI group （4.18 ± 0.95 pg/L） showed significantly higher plasma level of CD147 than control group （2.55 ± 0.29 pg/L） （P<0.01）. There was a significant difference in frequencies of alleles and genotypes in 3′UTR rs8259 of CD147 with three genotypes AA, AT and TT existed （P<0.05）. Logistic regression analysis for adjusting other risk factors displayed that AT genotypes （OR0.346, 95%CI: 0.210～0.569,P<0.05） and TT genotypes （OR0.107, 95%CI: 0.046～0.251, P<0.05） can decrease the relative risk of STEMI. Allele T carriers had low onset risk for STEMI （OR0.543, 95%CI: 0.404～0.730, P<0.05）, and allele A carriers had high risk for STEMI （OR1.841, 95%CI: 1.370～2.464, P<0.05）. The plasma level of CD147 was the highest in AA genotype （P<0.05）. Conclusions CD147 gene 3′UTR rs8259 allele A is probably the susceptible gene of STEMI. AA genotype can be at increased risk of STEMI due to enhancing the CD147 expression and allele T may be protective for STEMI.

Abstract:Aim To investigate the effect of ox-LDL on platelet extracellular matrix metalloproteinase inducer（EMMPRIN，CD147） release. Methods Washed platelets were incubated with ox-LDL （final concentrations of 25 mg/L, 50 mg/L or 100 mg/L ox-LDL, respectively）, PBS （as control） or 100 mg/L native LDL in vitro, and the expressions of CD147 and alpha-granule membrane glycoprotein （CD62P） on platelets were detected by flow cytometry. Soluble CD147 from the platelets was assessed by an enzyme-linked immunosorbent assay. Laser scanning microscopy （LSM） and transmission electron microscopy （TEM） were used to visualize the morphological changes and granule release, respectively, from the platelets. In parallel, the expression of CD147 on the platelets pre-incubated with anti-LOX-1 antibody was detected by flow cytometry. Results The CD147 relative mean fluorescence intensity （rMFI） from the groups of 25 mg/L, 50 mg/L or 100 mg/L ox-LDL （1.01±0.06，1.18±0.07, 1.24±0.08, respectively） were higher than that from the control group （0.86±0.10, both P<0.01） or native LDL group （0.89±0.11, both P<0.01）. The CD147 rMFI（0.96±0.08，1.05±0.07） from the platelets incubated with ox-LDL （50 mg/L or 100 mg/L） prior to pre-incubation with anti-LOX-1 antibody decreased compared with the 50 mg/L or 100 mg/L ox-LDL-treated platelets, respectively （both P<0.001）. After exposure to ox-LDL, morphological changes and granule release in the platelets were visualized by LSM and TEM. Conclusion ox-LDL induces the release of platelet CD147 via binding to LOX-1.