Oral amphipathic peptides as therapeutic agents.
Cholesterol can promote inflammation by its ability to stimulate the production of reactive oxygen species that result in the formation of pro-inflammatory oxidised phospholipids. High-density lipoproteins (HDLs) are part of the innate immune response and can be either pro- or anti-inflammatory independently of plasma HDL-cholesterol levels. During systemic inflammation as occurs with atherosclerosis, Apolipoprotein A-I can be altered, reducing its ability to promote reverse cholesterol transport and HDL can become pro-inflammatory. Amphipathic peptides with either a class A amphipathic helix (D-4F) or a class G* amphipathic helix (D-[113-122]apoJ), or even those that are too small to form a helix (KRES and FREL) have some similar characteristics. Their interaction with lipids leads to a reduction in lipoprotein-lipid hydroperoxides that releases HDL-associated antioxidant enzymes, such as paraoxonase, therefore providing antiatherosclerosis and anti-inflammatory activity. In addition, the peptide D-4F stimulates the formation and cycling of pre-beta HDL. These amphipathic peptides appear to have therapeutic potential as oral agents.
Reddy
Srinivasa T
ST
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-1679, USA. SReddy@mednet.ucla.edu
Anantharamaiah
G M
GM
Navab
Mohamad
M
Hama
Susan
S
Hough
Gregory
G
Grijalva
Victor
V
Garber
David W
DW
Datta
Geeta
G
Fogelman
Alan M
AM
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000737:chemistry; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D002784:Cholesterol / Q000276:immunology / Q000378:metabolism; D051152:Clusterin / Q000737:chemistry; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000276:immunology / Q000378:metabolism; D018716:Molecular Mimicry; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D017433:Protein Structure, Secondary
D000893:Anti-Inflammatory Agents; D016632:Apolipoprotein A-I; D051152:Clusterin; C465468:D-4F peptide; D008075:Lipoproteins, HDL; D010455:Peptides; D002784:Cholesterol