Borén J, Véniant M M, Young S G
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94141-9100, USA.
J Clin Invest. 1998 Mar 15;101(6):1197-202. doi: 10.1172/JCI1785.
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. [35S]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 BMS-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.
载脂蛋白B基因在人类心脏以及用人载脂蛋白B基因大基因组克隆构建的人载脂蛋白B转基因小鼠的心脏中表达。[35S]甲硫氨酸代谢标记实验表明,含载脂蛋白B100的脂蛋白由人心脏组织以及人载脂蛋白B转基因和非转基因小鼠心脏组织分泌。密度梯度分析显示,即使在脂蛋白脂肪酶抑制剂四氢脂抑素存在的情况下进行标记实验,大部分分泌的心脏脂蛋白仍是低密度脂蛋白。用微粒体甘油三酯转移蛋白(MTP)特异性抗血清进行的蛋白质免疫印迹表明,心脏微粒体含有MTP的97-kD亚基(参与脂质转移和脂蛋白组装的亚基)。在MTP抑制剂BMS-192951存在的情况下对小鼠心脏组织进行代谢标记,消除了心脏的脂蛋白分泌,但导致分泌了两种载脂蛋白B蛋白水解片段(80和120 kD),这些片段存在于密度梯度的底部部分。这些研究表明,不仅肝脏和肠道,心脏也分泌含载脂蛋白B的脂蛋白。我们推测,心脏分泌脂蛋白是一种从心脏清除多余脂质的机制。