Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases
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- Calabresi, L., Sirtori, C.R., Paoletti, R. et al. Curr Atheroscler Rep (2006) 8: 163. doi:10.1007/s11883-006-0054-4
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Apolipoprotein A-IMilano (apoA-IM) is a natural variant of apoA-I characterized by a cysteine for arginine substitution at position 173 of the primary sequence. ApoA-IM carriers have much less atherosclerosis than expected from their very low plasma high-density lipoprotein (HDL) cholesterol levels, suggesting that the variant might be protective. Synthetic HDL (sHDL) made with a recombinant form of the dimeric A-IM (A-IM/A-IM) and phospholipids given in single or multiple injections is effective in inducing the regression of atherosclerotic plaques, preventing arterial restenosis, and limiting cardiac dysfunction after ischemia/reperfusion injury. In a phase II trial in patients with acute coronary syndromes, a short-term treatment with A-IM/A-IM sHDL caused a remarkable reduction of atheroma burden. Although at early stages of drug development, A-IM/A-IM sHDL holds vast promise for the treatment of a variety of cardiovascular diseases in humans.