Heparin-binding EGF-like growth factor induces expression of lectin-like oxidized LDL receptor-1 in vascular smooth muscle cells

Atherosclerosis
Eri MukaiToru Kita

Abstract

Receptor-mediated endocytosis of oxidized LDL (Ox-LDL) has been implicated in lipid accumulation and vascular cell dysfunction. Lectin-like Ox-LDL receptor-1 (LOX-1) is highly inducible by proinflammatory cytokines, as well as angiotensin II and Ox-LDL in vitro. LOX-1 is expressed in macrophages and smooth muscle cells accumulated in the intima of advanced atherosclerotic plaques in vivo. Here we show that heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells, induces LOX-1 expression in cultured bovine aortic smooth muscle cells. HB-EGF (1-100 ng/ml) induced LOX-1 expression, which was peaked between 8 and 16 h after HB-EGF stimulation. HB-EGF-induced expression of LOX-1 was suppressed by ZD1839, an inhibitor of EGF receptor phosphorylation. Both MEK and p38 mitogen-activated protein kinase (MAPK) inhibitors significantly blocked LOX-1 upregulation induced by HB-EGF. Phosphatidylinositol 3-kinase (PI3K) inhibitors also blocked HB-EGF-induced LOX-1 expression. HB-EGF induced phosphorylation of ERK, p38 MAPK and Akt, which were suppressed by ZD1839. Upregulated expression of LOX-1 was associated with enhanced uptake of DiI-labeled Ox-LDL in smooth muscle cells. Tak...Continue Reading

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Citations

Sep 2, 2011·Cardiovascular Drugs and Therapy·Meiling YanChangping Hu
Aug 24, 2013·Journal of Hematology & Oncology·Jietang MaiXiao-Feng Yang
Dec 26, 2006·Circulation Journal : Official Journal of the Japanese Circulation Society·Kazuki NonakaTakahito Kondo
Dec 17, 2009·Journal of Atherosclerosis and Thrombosis·Teresa NavarraGiuseppina Basta
Aug 12, 2014·BioMed Research International·Felipe A ZunigaClaudio Aguayo
Nov 17, 2010·Fundamental & Clinical Pharmacology·Yiyi Sun, Xiuping Chen
Jan 26, 2006·Biochemical and Biophysical Research Communications·Hideyuki EtoChuwa Tei
Jun 4, 2016·Vascular Pharmacology·Natalia Di PietroAssunta Pandolfi
Jul 7, 2016·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Xiaoli RanXiuping Chen
Jan 11, 2017·Journal of Cellular Biochemistry·Cheng-I ChengYing-Hsien Kao
Dec 13, 2017·Infection and Immunity·Katarina KulhankovaWilmara Salgado-Pabón
Nov 6, 2018·International Heart Journal·Shota TsuchidaTetsuo Minamino
Jul 4, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Monique KerrochJean-Claude Dussaule
Nov 9, 2007·American Journal of Physiology. Renal Physiology·Jesus H DominguezRichard Peterson

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