Acute effects of high-density lipoproteins : biochemical basis and clinical findings

PURPOSE OF REVIEW: This review aims to provide an overview and an update of all therapeutic applications of synthetic high-density lipoproteins tested in animal models or in clinical trials. RECENT FINDINGS: Starting from 1990, when plasma-derived high-density lipoproteins were administered for the first time to cholesterol-fed rabbits to evaluate a possible atherosclerosis regression, the efficacy of high-density lipoprotein therapy has been assessed in a variety of cardiovascular diseases. Synthetic high-density lipoproteins constituted by purified apolipoprotein (apo)A-I, recombinant apoA-I variants or small apoA-I-mimetic peptides complexed with phospholipids have proven their efficacy in animal models and recently also in humans. Clinical investigations on the effects of acute HDL treatment have been focused only on atherosclerosis regression. Short-term administration of the mutant apoA-IMilano provided clearcut benefit in coronary atheromas. More recently, treatment with synthetic high-density lipoproteins containing human purified apoA-I was associated with moderate activity in atheroma regression, albeit with some safety concerns at high doses. SUMMARY: Administration of synthetic high-density lipoproteins has proven to be effective in promoting atherosclerosis regression not only in animal models, but also in humans. Applications to other areas of cardiovascular disease, such as restenosis and ischemia/reperfusion, have only, up to now, been tested in experimental models.