Focal accumulation of an apolipoprotein B-based synthetic oligopeptide in the healing rabbit arterial wall.
The functions of surface-accessible domains of apolipoprotein (apo) B, the protein moiety of low density lipoprotein (LDL), are unknown, aside from the LDL receptor-binding domain, which lies toward the carboxyl-terminal end of apoB. Since LDL accumulation in arterial lesions does not depend on recognition of LDLs by a cell-surface receptor, we synthesized an oligopeptide with the sequence of the trypsin-accessible domain of apoB that lies closest to the amino-terminal end of the protein and compared its biological activity to that of another synthetic oligopeptide with the sequence of the heparin- and apoB/apoE receptor-binding domains of apoE. (Tyrosine was added at the amino-terminal end of each peptide to facilitate radiolabeling.) The 18-amino acid apoB-based peptide included residues 1000-1016 of apoB, for which no function has been previously described. In radioautographs, the 125I-labeled peptide accumulated focally at the healing edges of regenerating endothelial islands in the balloon-catheter deendothelialized rabbit aorta. In contrast, the 21-residue apoE-based peptide, which included residues 129-148 of apoE, accumulated diffusely and uniformly throughout the deendothelialized areas of the aorta. The data show that focal binding of the apoB-based peptide can delineate arterial lesions and suggest that this arterial wall-binding domain of apoB mediates accumulation of LDLs in arterial lesions.
Shih
I L
IL
Division of Health Sciences and Technology, Harvard University, Boston, MA 02215.
Lees
R S
RS
Chang
M Y
MY
Lees
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001055:Apolipoproteins B / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism*; D011817:Rabbits; D014945:Wound Healing
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D007457:Iodine Radioisotopes; D010455:Peptides