An oral apoJ peptide renders HDL antiinflammatory in mice and monkeys and dramatically reduces atherosclerosis in apolipoprotein E-null mice.

نویسندگان

  • Mohamad Navab
  • G M Anantharamaiah
  • Srinivasa T Reddy
  • Brian J Van Lenten
  • Alan C Wagner
  • Susan Hama
  • Greg Hough
  • Eugene Bachini
  • David W Garber
  • Vinod K Mishra
  • Mayakonda N Palgunachari
  • Alan M Fogelman
چکیده

OBJECTIVE To determine the properties of a peptide synthesized from D-amino acids corresponding to residues 113 to 122 in apolipoprotein (apo) J. METHODS AND RESULTS In contrast to D-4F, D- [113-122]apoJ showed minimal self-association and helicity in the absence of lipids. D-4F increased the concentration of apoA-I with pre-beta mobility in apoE-null mice whereas D- [113-122]apoJ did not. After an oral dose D- [113-122]apoJ more slowly associated with lipoproteins and was cleared from plasma much more slowly than D-4F. D- [113-122]apoJ significantly improved the ability of plasma to promote cholesterol efflux and improved high-density lipoprotein (HDL) inflammatory properties for up to 48 hours after a single oral dose in apoE-null mice, whereas scrambled D- [113-122]apoJ did not. Oral administration of 125 microg/mouse/d of D- [113-122]apoJ reduced atherosclerosis in apoE-null mice (70.2% reduction in aortic root sinus lesion area, P=4.3 x 10(-13); 70.5% reduction by en face analysis, P=1.5 x 10(-6)). In monkeys, oral D- [113-122]apoJ rapidly reduced lipoprotein lipid hydroperoxides (LOOH) and improved HDL inflammatory properties. Adding 250 ng/mL of D-[113-122]apoJ (but not scrambled D- [113-122]apoJ) to plasma in vitro reduced LOOH and increased paraoxonase activity. CONCLUSIONS Oral D- [113-122]apoJ significantly improves HDL inflammatory properties in mice and monkeys and inhibits lesion formation in apoE-null mice.

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Oral small peptides render HDL antiinflammatory in mice and monkeys and reduce atherosclerosis in ApoE null mice.

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عنوان ژورنال:
  • Arteriosclerosis, thrombosis, and vascular biology

دوره 25 9  شماره 

صفحات  -

تاریخ انتشار 2005