Immune-complex-mediated vasculitis increases coronary artery lipid accumulation in autoimmune-prone MRL mice.
MRL/lpr mice develop severe autoimmune disease and vasculitis by 5 months of age, whereas congenic strain MRL/n mice exhibit much milder vasculitis with a later age of onset. When maintained on a high-fat, high-cholesterol (atherogenic) diet, strain MRL/lpr mice exhibited a striking deposition of lipid in both the large and small coronary arteries, whereas strain MRL/n mice exhibited very little lipid accumulation. Neither strain exhibited lipid accumulation on a low-fat chow diet. The atherogenic diet induced hyperlipidemia in both strains, but surprisingly the levels of atherogenic apolipoprotein B-containing lipoproteins were much lower in MRL/lpr mice. Immunohistochemical studies revealed that immune complexes (immunoglobulins G and M), T and B lymphocytes, macrophages, granulocytes, apolipoprotein B, and serum amyloid A proteins were present in the walls of the coronary arteries that had vasculitis and lipid accumulation. By 6-7 months of age, MRL/lpr mice had a higher incidence of myocardial infarction in the atherogenic diet group (53%) compared with the chow group (14%), whereas MRL/n mice exhibited no myocardial infarction on either diet. These results suggest important interactions between vasculitis, hyperlipidemia, and arterial lipid accumulation. They support the concept that injury to the vessel wall in immune-complex-mediated vasculitis increases lipid deposition in the presence of hyperlipidemia.
Qiao
J H
JH
Department of Medicine, UCLA 90024.
Castellani
L W
LW
Fishbein
M C
MC
Lusis
A J
AJ
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology; D003331:Coronary Vessels / Q000737:chemistry* / Q000276:immunology / Q000473:pathology; D004036:Diet, Atherogenic; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D009203:Myocardial Infarction / Q000150:complications; D000685:Serum Amyloid A Protein / Q000032:analysis; D013601:T-Lymphocytes / Q000473:pathology; D014657:Vasculitis / Q000150:complications / Q000276:immunology*
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008074:Lipoproteins; D000685:Serum Amyloid A Protein