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High‐density lipoprotein Mimetic peptide 4F acts on the intestinal microbiota and reduces systemic inflammation (LB533)
Author(s) -
Pourtabatabaei Nasim,
Shabihkhani Maryam,
Vakili Ladan,
Navab Kaveh,
Barseghian Zarina,
Seddigh Farhad,
Hough Greg
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb533
Subject(s) - chemistry , arachidonic acid , peptide , inflammation , lipoprotein , lysophosphatidic acid , endocrinology , hydroxyeicosatetraenoic acid , linoleic acid , medicine , prostaglandin , eicosanoid , prostaglandin e2 , biochemistry , thromboxane , pharmacology , cholesterol , fatty acid , platelet , receptor , enzyme
High‐density lipoprotein (HDL) mimetic peptides have been studied in animals and humans for their ability to improve biomarkers of inflammation and for their ability to decrease atherosclerotic lesions or tumor burden in preclinical studies. The mechanism of action of these peptides is due to their remarkable ability to bind oxidized lipids including ox‐phospholipids, oxidized metabolites of arachidonic and linoleic acids, ox‐sterols and lysophosphatidic acids. Single oral doses of 4.3 and 7.14 mg/kg of the HDL mimetic peptide D‐4F significantly improved the HDL‐anti inflammatory index in patients with coronary heart disease compared with patients that received placebo. The intestine appears to be a major site of the action of the peptide. When Low‐density lipoprotein (LDL) R‐/‐ mice on Western Diet were treated with the peptide orally or by subcutaneous injection, the concentration of the peptide in the enterocytes was similar and plasma superoxide scavenging activity (SAA), lysophosphatidic acids, 5‐Hydroxyeicosatetraenoic acid (5‐HETE), 12‐HETE, 15‐HETE, 9‐Hydroxyoctadecadienoic acid (9‐HODE), 12‐HODE, Prostaglandin D2 (PGD2), PGE2 and Thromboxane B2 (TXB2) were similarly affected. Atherosclerotic lesions were also reduced to a similar extent.