Apo B100-containing lipoproteins are secreted by the heart

被引:103
作者
Borén, J
Véniant, MM
Young, SG
机构
[1] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA
[2] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94141 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94141 USA
关键词
lipoproteins; microsomal triglyceride transfer protein; myocardial lipids; transgenic mice; fatty acids;
D O I
10.1172/JCI1785
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The apo B gene is expressed in the human heart and in the hearts of human apo B transgenic mice generated with large genomic clones spanning the human apo B gene, [S-35]Methionine metabolic labeling experiments demonstrated that apo B100-containing lipoproteins are secreted by human heart tissue and by human apo B transgenic and nontransgenic mouse heart tissue. Density gradient analysis revealed that most of the secreted heart lipoproteins were LDLs, even when the labeling experiments were performed in the presence of tetrahydrolipstatin, an inhibitor of lipoprotein lipase, Western blots with a microsomal triglyceride transfer protein) (MTP)-specific antiserum demonstrated that the microsomes of the heart contain the 97-kD subunit of MTP (the subunit involved in the transfer of lipids and assembly of lipoproteins). Metabolic labeling of mouse heart tissue in the presence of EMS-192951, an MTP inhibitor, abolished lipoprotein secretion by the heart but resulted in the secretion of two apo B proteolytic fragments (80 and 120 kD), which were found in the bottom fraction of the density gradient, These studies reveal that the heart, and not just the liver and intestine, secretes apo B-containing lipoproteins. We speculate that lipoprotein secretion by the heart represents a mechanism for removing excess lipids from the heart.
引用
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页码:1197 / 1202
页数:6
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