C-terminal apolipoprotein E-derived peptide, Ep1.B, displays anti-atherogenic activity.
OBJECTIVE
Apolipoprotein E (ApoE) is a lipid transport protein with expanded functions in cellular responses to tissue injury, immune regulation and cell growth. ApoE directs vascular changes that contribute to arterial protection as evidenced by the fact that isoforms of ApoE and ApoE deficiency correlate closely with accelerated plaque growth. The N-terminus of the ApoE protein has well-characterized functions, displaying lipid-binding and anti-atherogenic activity, whereas the function of the C-terminus is only partially defined. We have assessed the effects of a 14 amino acid C-terminal ApoE peptide, termed Ep1.B (239-252), on intimal neoplasia in animal models. This peptide is a fragment of a naturally processed peptide (236-252) of murine ApoE.


RESULTS
Ep1.B injection reduced neointimal hyperplasia after vascular surgery in rats and mice. When given during early plaque progression in ApoE-deficient mice, Ep1.B injections also prevented plaque growth. Treatment with Ep1.B did not, however, reduce established plaque growth in older mice. Peptides with alanine substitution of amino acid 249, Ep1.N, and with complete sequence reversal, Ep1.R, did not consistently inhibit plaque growth.


CONCLUSIONS
A naturally processed C-terminal ApoE peptide, Ep1.B, has anti-atherogenic activity indicating a role for this naturally metabolized peptide in vascular wound healing and lipid homeostasis.
Bocksch
Leila
L
Vascular Biology Group, Robarts' Research Institute, Canada.
Rider
Beverly J
BJ
Stephens
Tracey
T
Dai
Erbin
E
Liu
Liying
L
Diao
Hong
H
Viswanathan
Kasinath
K
Munuswamy-Ramanujam
Ganesh
G
Singh
Bhagirath
B
Lucas
Alexandra
A
D017130:Angioplasty / Q000009:adverse effects; D000818:Animals; D001057:Apolipoproteins E / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000276:immunology / Q000293:injuries / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006965:Hyperplasia; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000473:pathology; D017539:Tunica Intima / Q000473:pathology
D001057:Apolipoproteins E; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; C524718:apolipoprotein E (239-252), mouse