Niemann Bernd, Rohrbach Susanne, Catar Rusan A, Muller Gregor, Barton Matthias, Morawietz Henning
Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, D-01307 Dresden, Germany.
Biochem Biophys Res Commun. 2005 Sep 2;334(3):747-53. doi: 10.1016/j.bbrc.2005.06.163.
This study addressed the question how different lipoproteins modulate the expression of endothelin-converting enzyme-1 (ECE-1) in human endothelial cells. The effect of native and oxidized low-density lipoproteins (nLDL, oxLDL) on expression of ECE-1, prepro-endothelin-1, and endothelin-1 peptide was studied in primary cultures of human endothelial cells. Native and oxidized LDL increased ECE-1 mRNA after 1 h, reaching its maximum at 100 microg/ml (1.9- and 2.5-fold, respectively). Furthermore, ECE-1 protein expression, prepro-endothelin-1 mRNA, and endothelin-1 peptide release were increased in response to nLDL or oxLDL. Induction of ECE-1 by nLDL and of prepro-endothelin-1 by oxLDL was reduced by protein kinase C inhibition. Increased expression of ECE-1 mRNA by oxLDL and of prepro-endothelin-1 by nLDL was blocked by an angiotensin II receptor type 1 antagonist. Our data provide evidence for a new mechanism how increased LDL plasma levels might contribute to enhanced endothelin-1 release in patients with hypercholesterolemia.
本研究探讨了不同脂蛋白如何调节人内皮细胞中内皮素转化酶-1（ECE-1）的表达这一问题。在人内皮细胞原代培养物中研究了天然和氧化型低密度脂蛋白（nLDL、oxLDL）对ECE-1、前内皮素原-1和内皮素-1肽表达的影响。天然和氧化型LDL在1小时后增加了ECE-1 mRNA，在100μg/ml时达到最大值（分别为1.9倍和2.5倍）。此外，响应nLDL或oxLDL，ECE-1蛋白表达、前内皮素原-1 mRNA和内皮素-1肽释放均增加。蛋白激酶C抑制可降低nLDL对ECE-1的诱导作用以及oxLDL对前内皮素原-1的诱导作用。1型血管紧张素II受体拮抗剂可阻断oxLDL对ECE-1 mRNA的增加表达作用以及nLDL对前内皮素原-1的增加表达作用。我们的数据为高胆固醇血症患者血浆LDL水平升高可能导致内皮素-1释放增加的新机制提供了证据。
