Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases.
Apolipoprotein A-I(Milano) (apoA-I(M)) is a natural variant of apoA-I characterized by a cysteine for arginine substitution at position 173 of the primary sequence. ApoA-I(M) 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-I(M) (A-I(M)/A-I(M)) 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-I(M)/A-I(M) sHDL caused a remarkable reduction of atheroma burden. Although at early stages of drug development, A-I(M)/A-I(M) sHDL holds vast promise for the treatment of a variety of cardiovascular diseases in humans.
Calabresi
Laura
L
Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milano, 20133 Milano, Italy. laura.calabresi@unimi.it
Sirtori
Cesare R
CR
Paoletti
Rodolfo
R
Franceschini
Guido
G
D000818:Animals; D016632:Apolipoprotein A-I / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D006801:Humans; D016896:Treatment Outcome
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; C080631:apolipoprotein A-I Milano