Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress

- Hypercholesterolemia leads to increased oxidative stress and lipid oxidation.
- Increased oxidative stress impairs arterial healing after injury.
- L-4F improves endothelial migration in vitro in presence of oxidized lipids.
- D4-F improves endothelial healing after carotid injury in hypercholesterolemic mice.
- ApoA-I mimetics may reduce thrombogenicity and restenosis of angioplasty sites.

ObjectiveEndothelial cell (EC) migration is essential for healing of arterial injuries caused by angioplasty, but a high cholesterol diet inhibits endothelial repair. In vivo studies suggest that apolipoprotein A-I (apoA-I), the major protein constituent of HDL, is essential for normal healing of arterial injuries. ApoA-I mimetics, including 4F, have been designed to mimic the amphipathic portion of the apoA-I molecule. This study was undertaken to determine if 4F improves endothelial migration and healing.MethodsA razor scrape assay was used to analyze the effect of 4F on EC migration in vitro. Endothelial healing in vivo was assessed following electrical injury of carotid arteries in mice. Markers of oxidative stress were also examined.ResultsLipid oxidation products inhibited EC migration in vitro, but preincubation with L-4F preserved EC migration. Endothelial healing of carotid arterial injuries in mice on a high cholesterol diet was delayed compared with mice on a chow diet with 27.8% vs. 48.2% healing, respectively, at 5 days. Administration of D-4F improved endothelial healing in mice on a high cholesterol diet to 43.4%. D-4F administration had no effect on lipid levels but decreased markers of oxidation. In vivo, there was a significant inverse correlation between endothelial healing and plasma markers of oxidative stress.ConclusionThese studies suggested that an apoA-I mimetic can improve endothelial healing of arterial injuries by decreasing oxidative stress.