Apolipoprotein A-I mimetic peptides.
Recent publications reveal the mechanism of action of apolipoprotein A-I (apoA-I) mimetic peptides to be the remarkable binding affinity that oxidized lipids have for these peptides compared with apoA-I. There was no difference in the binding affinity of oxidized lipids or in peptide efficacy in reducing inflammation and atherosclerosis in rabbits injected with peptides synthesized from all D- or all L-amino acids. The apoA-I mimetic peptide 4F increased the formation of pre-beta high-density lipoprotein, increased cholesterol efflux, and reduced lipoprotein oxidation in vitro; it increased antioxidants and vascular repair in type 1 diabetic rats; it improved vasodilation, oxidative stress, myocardial inflammation, and angiogenic potential in a mouse model of scleroderma; it reduced renal inflammation in low-density lipoprotein receptor-null mice fed a Western diet; it reduced arthritis in a rat model; it reduced adiposity, increased adiponectin levels, and improved insulin sensitivity in obese mice; and it improved high-density lipoprotein inflammatory properties in humans with coronary heart disease.
Van Lenten
Brian J
BJ
Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. bvanlent@mednet.ucla.edu
Wagner
Alan C
AC
Anantharamaiah
G M
GM
Navab
Mohamad
M
Reddy
Srinivasa T
ST
Buga
Georgette M
GM
Fogelman
Alan M
AM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D016632:Apolipoprotein A-I / Q000494:pharmacology* / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy; D050197:Atherosclerosis / Q000517:prevention & control; D008076:Cholesterol, HDL / Q000097:blood; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications; D009393:Nephritis / Q000188:drug therapy / Q000209:etiology; D009765:Obesity / Q000188:drug therapy; D012595:Scleroderma, Systemic / Q000188:drug therapy
D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL