Apolipoprotein A-I(Milano): current perspectives.
OBJECTIVE
Strategies to increase HDL are among the major targets of clinical research in atherosclerosis prevention. The mutant apolipoprotein A-I(Milano) has been associated with a reduced incidence of coronary disease in carriers. Furthermore, recombinant apolipoprotein A-I(Milano) has displayed remarkable atheroprotective activities and the possibility of directly reducing the burden of atherosclerosis in experimental models. This review is aimed at providing an update on the experimental studies in which apolipoprotein A-I(Milano), produced as a recombinant protein, has displayed important effects in the treatment of vascular diseases.


RESULTS
In the past year, two reports have appeared, indicating that a single-dose administration of recombinant apolipoprotein A-I(Milano) dimers formulated into liposomes can reduce atheromas in models such as the apolipoprotein E-deficient mice and a rabbit model of carotid focal lesion, in which a direct 90 min infusion of the product reduced atheroma up to 30%. This finding was associated with an increase in HDL free cholesterol and the permanence of the recombinant product in the lesion for over 72 h.


CONCLUSIONS
Recombinant apolipoprotein A-I(Milano), formulated as synthetic HDL with phospholipids, appears to exert a direct removing effect on arterial cholesterol. This is well evident in experimental animals and, more recently in clinical findings, as indicated by a dramatic increase in HDL free cholesterol after the infusion of different doses of the agent. As the product appears to be well tolerated and non-immunogenic, ongoing phase II studies in patients are being awaited with interest to obtain a 'proof of principle' for 'HDL therapy'.
Chiesa
Giulia
G
Department of Pharmacological Sciences, University of Milano, via Balzaretti 9, 20133, Milano, Italy. giulia.chiesa@unimi.it
Sirtori
Cesare R
CR
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism; D023903:Coronary Restenosis / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism
D016632:Apolipoprotein A-I; D011994:Recombinant Proteins