Role of fibrinopeptide B in early atherosclerotic lesion formation.
The development of atherosclerotic lesions involves many cell types, including macrophages. Fibrinopeptide B (FPB) has been shown to be a potent chemotactic agent for macrophages, which are abundant as intimal foam cells in atherosclerotic lesions, especially in cholesterol-fed rabbits. We hypothesize that intimal low-density lipoproteins also cause fibrinogen in the intima to release FPB and that FPB attracts macrophages in response to the high lipid levels associated with lesion development. To test our hypothesis, we used an atherosclerotic model. Silk sutures containing either FPB, fibrinopeptide A (FPA), lipopolysaccharide (LPS), or saline control were prepared. One suture of each type was placed in the adventitia of the femoral artery of a rabbit. Animals were killed at 1 or 2 weeks. Only vessels exposed to either FPB or LPS showed significant intimal thickening in the region adjacent to the suture site. Semi-thin electron microscopic sections indicated that the intimal wall was highly cellular and that many cells contained lipid vacuoles after 2 weeks. These sections also showed that the endothelium remained intact and that no injury to the media of the artery had occurred. Electron microscopy of the tissue samples showed the proliferation of smooth muscle cells and deposition of extracellular matrix in the 2-week animals, whereas foam cells were present in the 1-week animals. We conclude that FPB does indeed attract macrophages to the intima and that these macrophages may become foam cells. The model we have developed can be used to study possible mechanisms for the entry of macrophages into the intima during early lesion development and to further understand the complex interactions of FPB, fibrinogen, and lipids in atherosclerotic lesion development.
Singh
T M
TM
Department of Surgery, University of Chicago Hospitals, Illinois 60637.
Kadowaki
M H
MH
Glagov
S
S
Zarins
C K
CK
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005340:Fibrinogen / Q000502:physiology*; D005344:Fibrinopeptide A / Q000502:physiology; D005345:Fibrinopeptide B / Q000502:physiology*; D005487:Foam Cells / Q000502:physiology; D008070:Lipopolysaccharides / Q000502:physiology; D011817:Rabbits
D008070:Lipopolysaccharides; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D005340:Fibrinogen