title: High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides.
abstract: Numerous randomized clinical trials have established statins as the major standard therapy for atherosclerotic diseases because these molecules decrease the plasma level of low-density lipoprotein (LDL) cholesterol and moderately increase that of plasma high-density lipoprotein (HDL) cholesterol. The reverse cholesterol transport pathway, mediated by HDL particles, has a relevant antiatherogenic potential. An important approach to HDL-targeted therapy is optimization of the HDL-cholesterol level and enhanced removal of plasma cholesterol, together with the prevention and mitigation of inflammation related to atherosclerosis. Small-molecule inhibitors of cholesteryl ester transfer protein (CETP) increase the HDL-cholesterol level in subjects with normal or low HDL-cholesterol. However, CETP inhibitors do not seem to reduce the risk of atherosclerotic diseases. HDL therapies using reconstituted HDL, including apolipoprotein (Apo) A-I Milano, ApoA-I mimetics, or full-length ApoA-I, are dramatically effective in animal models. Of those, the ApoA-I-mimetic peptide called FAMP effectively removes cholesterol via the ABCA1 transporter and acts as an antiatherosclerotic agent by enhancing the biological functions of HDL without elevating the HDL-cholesterol level. Our review of the literature leads us to conclude that HDL-targeted therapies have significant atheroprotective potential and thus may effectively treat patients with cardiovascular diseases.
authors.affiliation: Department of Cardiology, Fukuoka University Hospital.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Uehara
authors.forename: Giulia
authors.initials: G
authors.lastname: Chiesa
authors.forename: Keijiro
authors.initials: K
authors.lastname: Saku
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000037:antagonists & inhibitors* / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D040761:Biomimetic Materials / Q000627:therapeutic use*; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D010455:Peptides / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010455:Peptides