OBJECTIVETo investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells.

METHODSTHP-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.

RESULTSCompared 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.

CONCLUSIONSScavenger 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.

Atorvastatin Calcium ; Cell Differentiation ; Cell Line ; Chemokine CCL2 ; metabolism ; Foam Cells ; cytology ; drug effects ; metabolism ; Heptanoic Acids ; pharmacology ; Humans ; Monocytes ; cytology ; drug effects ; metabolism ; Pyrroles ; pharmacology ; Scavenger Receptors, Class A ; metabolism

OBJECTIVETo investigate the effect of alpha-zearalenol on angiotensin II-induced beta3 integrin mRNA expression in human umbilical vein endothelial cells (HUVECs).

METHODSThe mRNA level in integrin beta3 was determined by reverse transcription-polymerase chain reaction. Endothelial NF-kappaB activity was determined by the luciferase activity assay of plasmid NF-kappaB-LUC.

RESULTSThe angiotensin II-induced beta3 integrin mRNA expression was inhibited by alpha-zearalenol and 17beta-estradiol (10 nmol/L -1 micromol/L), but not influenced by ICI 182, 780, a pure competitive antagonist for estrogen receptor or a nitric oxide inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. Alpha-zearalenol and 17beta-estradiol suppressed the angiotensin II-induced activation of NF-kappaB in endothelial cells.

CONCLUSIONAlpha-zearalenol inhibits angiotensin II-induced integrin beta3 mRNA expression by suppressing NF-kappaB activation in endothelial cells.

Angiotensin II ; antagonists & inhibitors ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; drug effects ; metabolism ; Estradiol ; pharmacology ; Female ; Gene Expression Regulation ; Humans ; Integrin beta3 ; biosynthesis ; genetics ; NF-kappa B ; antagonists & inhibitors ; physiology ; Nitric Oxide ; antagonists & inhibitors ; Phytoestrogens ; pharmacology ; RNA, Messenger ; metabolism ; Receptors, Estrogen ; antagonists & inhibitors ; Zeranol ; analogs & derivatives ; pharmacology