High-Density Lipoprotein-Targeted Therapy and Apolipoprotein A-I Mimetic Peptides

• Published in: Circulation Journal 2015/11/25, Vol.79(12), pp.2523-2528
• Main Authors: Uehara, Yoshinari, Chiesa, Giulia, Saku, Keijiro
• Format: Article
• Language: English
• Subjects: Animals; Apolipoprotein; Apolipoprotein A-I - antagonists & inhibitors; Apolipoprotein A-I - blood; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - drug therapy; Biomimetic Materials - therapeutic use; Cardiovascular disease; Cholesterol Ester Transfer Proteins - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Drug Delivery Systems - methods; Dyslipidemia; Humans; Peptides - therapeutic use; Randomized Controlled Trials as Topic; Reverse cholesterol transport
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.CJ-15-0960

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. (Circ J 2015; 79: 2523–2528)