Xianming Su1, Wei Yang, Xiaowen Zhi. 1. Department of Geriatric Cardiology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. suxianming2011@163.com
Abstract
OBJECTIVE: To study the effects of Danhong injection (DHI) on expression of the macrophage scavenger receptor 1 (MSR1) and ATP-binding cassette, sub-family A member 1 (ABCA1) genes, which encode scavenger receptor-A I (SR-AI) and ATP-binding cassette transporter 1 (ABCA1), respectively, as a potential anti-atherosclerotic mechanism. METHODS: Human U937 cells were stimulated by incubation with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 h. These stimulated, monocyte-like cells were then incubated for 24 h with 50 mg/L oxidized low-density lipoprotein (ox-LDL, to induce foam cell formation), together with a liver X receptor (LXR) agonist or with different DHI concentrations. MSR1 and ABCA1 mRNA levels were measured by fluorescence-based quantitative PCR. RESULTS: Compared with control cells (which received only ox-LDL), cells treated with both ox-LDL and 10 micromol/L LXR agonist showed lower MSR1 expression (but this effect was not statistically significant, P > 0.05) and higher ABCA1 expression (P < 0.01). Cells that received ox-LDL and 3 mL/L DHI possessed higher MSR1 mRNA levels than the controls, whereas cells treated with ox-LDL and higher DHI concentrations (10, 30 or 60 mL/L) showed lower MSR1 expression levels (but the differences observed between DHI concentration groups were not statistically significant, P > 0.05). ABCA1 expression in cells treated with ox-LDL and 3, 10 or 30 mL/L DHI was higher than in the control cells, and increased with increasing DHI concentration (P < 0.05). ABCA1 expression in cells treated with ox-LDL and the highest DHI concentration tested (60 mL/L) was not significantly different from that in the controls. ABCA1 mRNA levels in cells treated with ox-LDL and DHI were similar to, or lower than, those in cells treated with ox-LDL and the LXR agonist. CONCLUSION: DHI does not affect MSR1 mRNA levels in ox-LDL-treated U937 cells. However, at certain concentrations (10 and 30 mL/L), DHI significantly increases ABCA1 mRNA levels. Therefore, the anti-atherosclerotic action of DHI might be mediated by an increased expression of ABCA1.
OBJECTIVE: To study the effects of Danhong injection (DHI) on expression of the macrophage scavenger receptor 1 (MSR1) and ATP-binding cassette, sub-family A member 1 (ABCA1) genes, which encode scavenger receptor-A I (SR-AI) and ATP-binding cassette transporter 1 (ABCA1), respectively, as a potential anti-atherosclerotic mechanism. METHODS:Human U937 cells were stimulated by incubation with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 h. These stimulated, monocyte-like cells were then incubated for 24 h with 50 mg/L oxidized low-density lipoprotein (ox-LDL, to induce foam cell formation), together with a liver X receptor (LXR) agonist or with different DHI concentrations. MSR1 and ABCA1 mRNA levels were measured by fluorescence-based quantitative PCR. RESULTS: Compared with control cells (which received only ox-LDL), cells treated with both ox-LDL and 10 micromol/L LXR agonist showed lower MSR1 expression (but this effect was not statistically significant, P > 0.05) and higher ABCA1 expression (P < 0.01). Cells that received ox-LDL and 3 mL/L DHI possessed higher MSR1 mRNA levels than the controls, whereas cells treated with ox-LDL and higher DHI concentrations (10, 30 or 60 mL/L) showed lower MSR1 expression levels (but the differences observed between DHI concentration groups were not statistically significant, P > 0.05). ABCA1 expression in cells treated with ox-LDL and 3, 10 or 30 mL/L DHI was higher than in the control cells, and increased with increasing DHI concentration (P < 0.05). ABCA1 expression in cells treated with ox-LDL and the highest DHI concentration tested (60 mL/L) was not significantly different from that in the controls. ABCA1 mRNA levels in cells treated with ox-LDL and DHI were similar to, or lower than, those in cells treated with ox-LDL and the LXR agonist. CONCLUSION:DHI does not affect MSR1 mRNA levels in ox-LDL-treated U937 cells. However, at certain concentrations (10 and 30 mL/L), DHI significantly increases ABCA1 mRNA levels. Therefore, the anti-atherosclerotic action of DHI might be mediated by an increased expression of ABCA1.