OBJECTIVETo investigate the importance of the specific structure of L-4F, an apolipoprotein A-1 mimetic, in inhibiting atherosclerosis. The study was designed to compare the effect of L-4F and scramble-4F (SC-4F) in preventing low density lipoprotein (LDL) induced endothelial cell dysfunction. L-4F and SC-4F has the same amino acids but different nucleotide sequence.

METHODSBovine aortic endothelial cells (BAEC) were incubated with single L-4F 10 microg/ml or SC-4F 10 microg/ml, or LDL 6.2 mmol/L in the absence or presence of L-4F 10 microg/ml or SC-4F 10 microg/ml for 24 h and assayed for (1) changes of superoxide anion (O2-*) generation in BAEC by superoxide dismutase (SOD)-inhibitable ferricytochrome C reduction, and (2) the production of nitric oxide (NO) in BAEC by ozone chemiluminescence with VCL3.

RESULTS(1) L-4F and SC-4F themselves had no affect on BAEC O2-* generation. (2) LDL significantly increased O2-* generation in BAEC and LDL-induced O2-* generation was inhibited by pretreatment of LDL with L-4F. However, pretreatment of LDL with SC-4F had no effect on inhibition of LDL-induced O2-* generation. (3) LDL significantly inhibited NO generation in BAEC and pretreatment of LDL with L-4F could inhibit LDL-induced decrease of NO generation, but pretreatment of LDL with SC-4F still inhibited NO generation in BAEC.

CONCLUSIONL-4F can prevent LDL induced endothelial cell dysfunction by maintaining the balance of NO and O2-*, but SC-4F doesn't. It suggests that the specific structure of L-4F may play a crucial role in preventing atherosclerosis and it may provide a new clue for searching a novel approach on prevention and therapeutics of atherosclerosis in the future.

Animals ; Atherosclerosis ; prevention & control ; Cattle ; Cells, Cultured ; Endothelial Cells ; drug effects ; physiology ; Lipoproteins, LDL ; antagonists & inhibitors ; Nitric Oxide ; biosynthesis ; Peptides ; pharmacology ; Superoxides ; metabolism