C-terminal apolipoprotein E-derived peptide, Ep1.B, displays anti-atherogenic activity.

Abstract

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.

METHODS AND 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.

CONCLUSION:

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.

• Authors: Leila Bocksch, Beverly J Rider, Tracey Stephens, Erbin Dai, Liying Liu, Hong Diao, Kasinath Viswanathan, Ganesh Munuswamy-Ramanujam, Bhagirath Singh, Alexandra Lucas
• Journal: Atherosclerosis (Atherosclerosis) Vol. 194 Issue 1 Pg. 116-24 (Sep 2007) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 17126342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Histocompatibility Antigens Class II
• Peptide Fragments
• apolipoprotein E (239-252), mouse

Topics

• Angioplasty (adverse effects)
• Animals
• Apolipoproteins E (chemical synthesis, chemistry, genetics, metabolism, pharmacology)
• Atherosclerosis (drug therapy, immunology, pathology)
• Carotid Artery Injuries (immunology, pathology)
• Disease Models, Animal
• Female
• Femoral Artery (immunology, injuries, pathology)
• Histocompatibility Antigens Class II (metabolism)
• Hyperplasia
• Iliac Artery (injuries, pathology)
• Macrophages (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Peptide Fragments (chemical synthesis, metabolism, pharmacology)
• Protein Structure, Tertiary
• Rats
• Rats, Sprague-Dawley
• T-Lymphocytes (pathology)
• Tunica Intima (pathology)