Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes

Abstract

In a small village in northern Italy called Limone sul Garda live approximately 40 carriers with a naturally occurring variant of apolipoprotein A-I known as ApoA-I Milano. Individuals with ApoA-I Milano are characterized by very low levels of high-density lipoprotein cholesterol (HDL-C) (10-30 mg/dL [0.25-0.78 mmol/L]), apparent longevity,¹ and much less atherosclerosis than expected for their HDL-C levels.² The ApoA-I Milano protein differs from native ApoA-I in that cysteine is substituted at position 173 for arginine allowing disulfide-linked dimer formation. Recombinant ApoA-I Milano has been formulated in a complex with a naturally occurring phospholipid to mimic the properties of nascent HDL (ETC-216, Esperion Therapeutics, Ann Arbor, Mich). Studies in mice and rabbits with experimental atherosclerosis have demonstrated that rApoA-I Milano/phospholipid complexes rapidly mobilize cholesterol and thereby reduce atherosclerotic plaque burden. The antiatherosclerotic effects (reductions in plaque lipid and macrophage content) occur in animals as rapidly as 48 hours after a single infusion.³