Proatherogenic high-density lipoprotein, vascular inflammation, and mimetic peptides.
Atherosclerosis is an example of an inflammatory disorder. During the acute phase and under inflammatory conditions, high-density lipoprotein (HDL), which is normally anti-inflammatory, can become proinflammatory. Reactive oxygen species generated by several enzyme systems can modify phospholipids and sterols, producing oxidized phospholipids and oxidized sterols that reduce the capacity of HDL to protect against undesirable oxidative modifications of molecules. In animal models of dyslipidemia, diabetes, vascular inflammation, and chronic rejection, it is observed that reducing oxidative and inflammatory pressure will help HDL regain its protective role. One way to accomplish this is through the use of apolipoprotein A-I mimetic peptides, which remove oxidation products from lipoproteins and cell membranes, returning normal structure and function to low-density lipoprotein and HDL. These mimetic peptides markedly reduce atherosclerosis in animal models. Published studies of apolipoprotein mimetic peptides in models of inflammatory disorders other than atherosclerosis suggest that they have efficacy in a wide range of inflammatory conditions.
Yu
Roger
R
Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Yekta
Babak
B
Vakili
Ladan
L
Gharavi
Navid
N
Navab
Mohamad
M
Marelli
Daniel
D
Ardehali
Abbas
A
D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology / Q000502:physiology*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006084:Graft Rejection / Q000503:physiopathology; D016027:Heart Transplantation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D007378:Interleukins / Q000097:blood; D007674:Kidney Diseases / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D010455:Peptides / Q000494:pharmacology
D016632:Apolipoprotein A-I; D008078:Cholesterol, LDL; C465468:D-4F peptide; D007378:Interleukins; D008075:Lipoproteins, HDL; D010455:Peptides