Metabolism of triglyceride-rich lipoproteins and their role in atherosclerosis.
Recent large-scale clinical trials indicate that hypertriglyceridemia is a risk factor in coronary artery disease; however, the mechanism has not yet been completely clarified. We are currently studying the metabolism of triglyceride-rich lipoproteins and their role in atherosclerosis. Remnants, one of atherogenic lipoproteins, showed a marked increase and remained high even 8 hours after fat loading, especially in patients with coronary artery disease or diabetes mellitus. This shows that the postprandial state persists almost the whole day in these patients. Accordingly, it may be important to assess post-prandial remnant concentrations when evaluating risk factors for atherosclerosis. We identified apo B100 expression in the epithelial cells of the small intestine by immunoblotting with anti-apo B100 monoclonal antibody and dot-blotting of PCR-amplified cDNA. This indicates that not only apo B48, but also apo B100 is expressed in human small intestinal epithelium. The expression of apo B100 suggests that dietary VLDL may be synthesized in human small intestinal epithelium and converted into LDL, which may play an important role in atherosclerosis. A new receptor, apo B48, which binds and internalizes triglyceride-rich lipoproteins via a domain in apo B48, was identified in human monocyte-macrophages. The receptor differs from the scavenger receptor family and LDL receptor family because it does not bind acetyl LDL and it does bind VLDL devoid of apo E. Immunohistochemical studies indicate colocalization of anti-apo B48 receptor antibody in human atherosclerotic lesion foam cells, suggesting that apo B48 receptor may contribute to foam cell formation and atherosclerosis.
Tanaka
A
A
Department of Internal Medicine, Tokyo Medical and Dental University, Japan. tanaka.med3@tmd.ac.jp
AI
M
M
Kobayashi
Y
Y
Tamura
M
M
Shimokado
K
K
Numano
F
F
D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D018110:Receptors, Lipoprotein / Q000502:physiology*; D012307:Risk Factors; D014280:Triglycerides / Q000502:physiology*
D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C411291:apo B48 receptor; C030106:very low density lipoprotein triglyceride