Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice.
LDL receptor-deficient (LDLR(-/-)) mice exhibit mild hyperlipidemia on a chow diet but develop severe hyperlipidemia on a high fat diet. In this study, we investigated neointimal formation after removal of the endothelium when LDLR(-/-) mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. At 10 weeks of age, female mice underwent endothelial denudation of the left common carotid artery. Two weeks after injury, neointimal formation was barely detectable in the injured vessel when mice developed mild hyperlipidemia on the chow diet. In contrast, neointimal lesions were obvious when mice developed severe hyperlipidemia on the Western diet. Immunohistochemical and histological analyses demonstrated the presence of macrophage foam cells and smooth muscle cells in neointimal lesions. The injured artery also exhibited a significant increase in medial area on the Western diet. Plasma levels of MCP-1 and soluble VCAM-1 were significantly elevated by feeding of the Western diet. These data indicate that hyperlipidemia aggravates neointimal growth in LDLR(-/-) mice by promoting foam cell formation and inflammation.
Tian
Jing
J
Department of Radiology, University of Virginia, Charlottesville, VA 22908, USA.
Pei
Hong
H
Sanders
John M
JM
Angle
John F
JF
Sarembock
Ian J
IJ
Matsumoto
Alan H
AH
Helm
Gregory A
GA
Shi
Weibin
W
D000821:Animal Feed; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005260:Female; D005487:Foam Cells / Q000378:metabolism; D006949:Hyperlipidemias / Q000235:genetics* / Q000473:pathology*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology*; D017539:Tunica Intima / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008055:Lipids; D011973:Receptors, LDL; D019010:Vascular Cell Adhesion Molecule-1