TY - JOUR
T1 - C-terminal apolipoprotein E-derived peptide, Ep1.B, displays anti-atherogenic activity
AU - Bocksch, Leila
AU - Rider, Beverly J.
AU - Stephens, Tracey
AU - Dai, Erbin
AU - Liu, Liying
AU - Diao, Hong
AU - Viswanathan, Kasinath
AU - Munuswamy-Ramanujam, Ganesh
AU - Singh, Bhagirath
AU - Lucas, Alexandra
N1 - Funding Information:
This research was supported by grants from the Canadian Institutes for Health Research (CIHR) and the Heart and Stroke Foundation of Ontario (HSFO). We would like to thank Joan Fleming for her assistance in collating and typing this manuscript and Edwin Lee-Chan for synthesis and purification of peptides used in this study.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Apolipoprotein E (ApoE)
KW - Atherosclerosis
KW - Lipids
KW - Major histocompatibility complex II (MHC II)
KW - Neointima
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U2 - 10.1016/j.atherosclerosis.2006.10.014
DO - 10.1016/j.atherosclerosis.2006.10.014
M3 - Article
C2 - 17126342
AN - SCOPUS:34648843007
SN - 0021-9150
VL - 194
SP - 116
EP - 124
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -