PURPOSE OF REVIEW: Peptides that resemble in physicochemical properties the helices of apoprotein A-I, the major protein of atheroprotective HDL, show promise for the treatment of atherosclerosis-related vascular disease. The properties and promise of these so-called mimetic peptides will be explored in this review. RECENT FINDINGS: Both HDL and mimetic peptides are able to scavenge and sequester oxidized lipids and hence protect endothelial cells and arteries from the pro-inflammatory action of oxidized LDL. Active mimetic peptides have an amphipathic alpha-helical secondary structure, whose hydrophobic face is particularly important for its bioactivity. The most frequently employed peptide is 4F. The comparative bioactivity of variants of 4F, particularly tandem helical peptides, has been explored. The recent observation of the very high affinity of bioactive peptides for oxidized fatty acids and phospholipids provides a likely mechanism for the action of these peptides in inhibiting early atherosclerosis formation. It is not clear that these peptides alone are effective in reversing established atherosclerosis, although they may achieve this outcome in synergy with statin therapy. SUMMARY: Recent observations of mimetic peptides have pointed to promising therapies for patients with cardiovascular disease. The peptides appear to be well tolerated and effective in promoting the anti-inflammatory properties of HDL.
PURPOSE OF REVIEW: Peptides that resemble in physicochemical properties the helices of apoprotein A-I, the major protein of atheroprotective HDL, show promise for the treatment of atherosclerosis-related vascular disease. The properties and promise of these so-called mimetic peptides will be explored in this review. RECENT FINDINGS: Both HDL and mimetic peptides are able to scavenge and sequester oxidized lipids and hence protect endothelial cells and arteries from the pro-inflammatory action of oxidized LDL. Active mimetic peptides have an amphipathic alpha-helical secondary structure, whose hydrophobic face is particularly important for its bioactivity. The most frequently employed peptide is 4F. The comparative bioactivity of variants of 4F, particularly tandem helical peptides, has been explored. The recent observation of the very high affinity of bioactive peptides for oxidized fatty acids and phospholipids provides a likely mechanism for the action of these peptides in inhibiting early atherosclerosis formation. It is not clear that these peptides alone are effective in reversing established atherosclerosis, although they may achieve this outcome in synergy with statin therapy. SUMMARY: Recent observations of mimetic peptides have pointed to promising therapies for patients with cardiovascular disease. The peptides appear to be well tolerated and effective in promoting the anti-inflammatory properties of HDL.
Authors: Masashi Suzuki; David K Pritchard; Lev Becker; Andrew N Hoofnagle; Natsuko Tanimura; Theo K Bammler; Richard P Beyer; Roger Bumgarner; Tomas Vaisar; Maria C de Beer; Frederick C de Beer; Kensuke Miyake; John F Oram; Jay W Heinecke Journal: Circulation Date: 2010-10-25 Impact factor: 29.690
Authors: Geoffrey D Wool; Veneracion G Cabana; John Lukens; Peter X Shaw; Christoph J Binder; Joseph L Witztum; Catherine A Reardon; Godfrey S Getz Journal: FASEB J Date: 2010-09-27 Impact factor: 5.191
Authors: David Meriwether; Dawoud Sulaiman; Alan Wagner; Victor Grijalva; Izumi Kaji; Kevin J Williams; Liqing Yu; Spencer Fogelman; Carmen Volpe; Steven J Bensinger; G M Anantharamaiah; Ishaiahu Shechter; Alan M Fogelman; Srinivasa T Reddy Journal: J Lipid Res Date: 2016-05-19 Impact factor: 5.922