PubMed · 9644999
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K Kajinami, A Nohara, Y Tohdoh, H Mabuchi. 1998. [Abnormal apolipoprotein B].. https://pubmed.ncbi.nlm.nih.gov/9644999/
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Type 2 diabetes is associated with a marked increase in the risk of coronary artery disease. Dyslipidemia is believed to be a major source of this increased risk. Several studies in diabetic patients have demonstrated a decreased incidence of coronary artery disease with the use of drugs that lower the level of low-density lipoprotein in diabetic patients, but other forms of dyslipidemia, such as hypertriglyceridemia, are believed to play a role in the etiology of coronary artery disease in diabetes. Drugs, such as fenofibrate, which improve these other forms of dyslipidemia, are being investigated in diabetic patients to determine if they decrease mortality and morbidity from coronary artery disease.
Much of the cholesterol that accumulates in atherosclerotic plaques is found within monocyte-macrophages transforming these cells into "foam cells." Native low density lipoprotein (LDL) does not cause foam cell formation. Treatment of LDL with cholesterol esterase converts LDL into cholesterol-rich liposomes having >90% cholesterol in unesterified form. Similar cholesterol-rich liposomes are found in early developing atherosclerotic plaques surrounding foam cells. We now show that cholesterol-rich liposomes produced from cholesterol esterase-treated LDL can cause human monocyte-macrophage foam cell formation inducing a 3-5-fold increase in macrophage cholesterol content of which >60% is esterified. Although cytochalasin D inhibited LDL liposome-induced macrophage cholesteryl ester accumulation, LDL liposomes did not enter macrophages by phagocytosis. Rather, the LDL liposomes induced and entered surface-connected compartments within the macrophages, a unique endocytic pathway in these cells that we call patocytosis. LDL liposome apoB rather than LDL liposome lipid mediated LDL liposome uptake by macrophages. This was shown by the findings that: 1) protease treatment of the LDL liposomes prevented macrophage cholesterol accumulation; 2) liposomes prepared from LDL lipid extracts did not cause macrophage cholesterol accumulation; and 3) purified apoB induced and accumulated within macrophage surface-connected compartments. Although apoB mediated the macrophage uptake of LDL liposomes, this uptake did not occur through LDL, LDL receptor-related protein, or scavenger receptors. Also, LDL liposome uptake was not sensitive to treatment of macrophages with trypsin or heparinase. Cholesterol esterase-mediated transformation of LDL into cholesterol-rich liposomes is an LDL modification that: 1) stimulates uptake of LDL cholesterol by apoB-dependent endocytosis into surface-connected compartments, and 2) causes human monocyte-macrophage foam cell formation.