Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.

Abstract

Apo A-I M significantly reduced intimal thickening and macrophage content after balloon injury in cholesterol-fed rabbits without a change in arterial total cholesterol content. Although the precise mechanism of action remains to be defined, these findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications.

Lipoprotein-like Phospholipid Particles Inhibit the Smooth Muscle Cell Cytotoxicity of Lysophosphatidycholine and Platelet-Activating Factor

“…37 We have previously shown that apoA-I Milano inhibits the formation of intimal lesions after balloon injury of the aorta in hypercholesterolemic rabbits. 38 This inhibition was associated with a reduced intimal inflammatory activity (assessed by a decreased number of intimal macrophages) but not with a decreased level of aortic tissue cholesterol. These findings suggest that apoA-I Milano may have functioned by scavenging proinflammatory phospholipid species rather than by the removal of cholesterol from the vessel wall of the hypercholesterolemic animals.…”

Cardiovascular Status of Carriers of the Apolipoprotein A-I Milano Mutant

“…29 More recent data demonstrate that the apoA-I M dimer is most likely the "protective" component, characterized by a very slow turnover in both the carriers and normal volunteers 29 and by a high efficiency in promoting cell cholesterol efflux. 30 A recombinant version of apoA-I M / apoA-I M , 31 administered as a phospholipid complex, has been shown to significantly reduce vascular stenosis after balloon angioplasty 32 or periarterial manipulation 33 in cholesterol-fed rabbits, to prevent or reduce atheroma formation in apoEdeficient mice, 34 and to delay thrombus formation in rats. 35 In conclusion, a detailed series of cardiovascular studies investigating a group of carriers of the apoA-I M mutant characterized by extreme reductions of HDL cholesterol indicates that despite an atherogenic lipoprotein profile, they do not show any clear evidence of vascular disease at the preclinical level.…”

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…However, the highest degree of endothelial turnover is likely observed after arterial injury, in allografts (Rahmani et al 2006), and in vein grafts. Although there is significant evidence that HDLs exert beneficial effects in models of angioplasty-or injury-induced arteriosclerosis (Ameli et al 1994;De Geest et al 1997;Shah and Amin 1992), we will focus here on allograft vasculopathy and vein graft atherosclerosis.…”