Abstract 1737: FoxO4 is an Atheroprotective Factor
Atherosclerosis is a chronic inflammatory process of arterial wall as the result of interactions between genetic and environmental factors. The pathological change of atherosclerosis involves interactions of endothelial cells, smooth muscle cells and infiltrating immune cells including macrophages and T cells. We have found that one of the family members of FoxO transcription factor, FoxO4, plays important roles in the regulation of phenotype switch of smooth muscle cells, matrix remodeling, and immune cell recruitment. Based on these observations, we hypothesize that FoxO4 may regulate atherogenesis through one or more aforementioned processes. To test this hypothesis, we generated ApoE/Foxo4 double knockout mice (DKO). The ApoE/Foxo4 DKO mice and ApoE single knockout littermates (SKO) were fed with high fat diet for 8 weeks to induce atherosclerosis. At the end of the 8 weeks, the aortas and hearts were dissected out and plasmas were collected. The aortic plaque was stained with Oil Red O en face and the percentage of plaque area to aortic face area was determined. Results show that there was no difference of plasma cholesterol level between DKO mice and control group (2300 ± 414mg/L in ApoE group vs 2667 ± 344mg/L in ApoE/Foxo4 DKO group, p = 0.28). No body weight difference was observed between these two groups of mice neither before nor after high fat diet. ApoE/Foxo4 DKO mice developed significantly more atheroscle-rotic plaques than that of ApoE SKO littermate controls (6.28 ± 1.40 in ApoE SKO group vs 9.47 ± 2.59 in ApoE/Foxo4 DKO group, p = 0.0016), suggesting that FoxO4 is an atheroprotective factor. We are currently investigating the molecular mechanism(s) by which FoxO4 regulates atherogenesis.
This research has received full or partial funding support from the American Heart Association, AHA National Center.