Karikó K, Rosenbaum H, Kuo A, Zurier R B, Barnathan E S
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6060.
FEBS Lett. 1995 Mar 13;361(1):118-22. doi: 10.1016/0014-5793(95)00170-e.
To determine whether unsaturated fatty acids induce changes in the mRNA level of plasminogen activator inhibitor type-1 (PAI-1), Northern analyses were performed on human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells that were treated with two common fatty acids. Supplementation of cultured HUVEC with docosahexanoic acid (DHA) or with dihomogamma linolenic acid (DGLA), resulted in a concentration dependent, specific increase of the PAI-1 transcript levels, which was detectable within 2 h. DHA and DGLA treatment of smooth muscle cells did not result in changes in the PAI-1 mRNA levels. Homology search of the upstream regulatory region of the PAI-1 gene sequences identified a consensus nucleotide sequence for a fatty acid-responsive element. Our results indicate that unsaturated fatty acids selectively increase PAI-1 mRNA levels in endothelial cells, the primary source of circulating PAI-1 in vivo.
为了确定不饱和脂肪酸是否会诱导1型纤溶酶原激活物抑制剂（PAI-1）的mRNA水平发生变化，我们对用两种常见脂肪酸处理过的人脐静脉内皮细胞（HUVEC）和血管平滑肌细胞进行了Northern分析。用二十二碳六烯酸（DHA）或二高γ-亚麻酸（DGLA）补充培养的HUVEC，会导致PAI-1转录水平呈浓度依赖性、特异性增加，在2小时内即可检测到。DHA和DGLA处理平滑肌细胞不会导致PAI-1 mRNA水平发生变化。对PAI-1基因序列上游调控区域进行同源性搜索，确定了一个脂肪酸反应元件的共有核苷酸序列。我们的结果表明，不饱和脂肪酸可选择性地增加内皮细胞中PAI-1的mRNA水平，内皮细胞是体内循环PAI-1的主要来源。
