期刊
JOURNAL OF LIPID RESEARCH
卷 50, 期 3, 页码 364-375出版社
ELSEVIER
DOI: 10.1194/jlr.M800215-JLR200
关键词
hypercholesterolemia; endothelial function; hypertension
资金
- Fondo de Investigacion Sanitaria [FIS 01/3057]
- Ministerio de Ciencia y Tecnologia [SAF2004-07845, SAF 2005-06025]
- Comunidad de Madrid [GR/SAL/0320/2004]
- Fundacion Mutua Madrilena [CC-FMM05]
- program Redes tematicas de investigacion cooperativa (RedinRed) del Instituto de Salud Carlos III [ISCIII-RETIC RD06/0016/0002]
The aim of our study was to analyze the relationships between atherosclerosis and endothelin-converting enzyme-1 (ECE-1). Four-week-old C57BL/6J [wild-type (WT)] and apolipoprotein E-deficient (apoE) mice were fed with a standard or Western-type fat diet for 8 wks. ApoE showed atherosclerotic lesions in the aorta, higher blood pressure and vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein content than WT. ApoE showed a significant increase in ECE-1 protein content and mRNA expression in aorta, lung, and kidney, without changes in heart. When an ECE-1 inhibitor, FR-901533, was administered to them, blood pressure decreased in apoE on fat diet versus apoE on normal diet and WT. ECE-1 and LOX-1 protein content were elevated in peripheral blood mononuclear cells (PBMC) from hypercholesterolemic patients. In order to study the mechanism involved in this ECE-1 up-regulation, bovine aortic endothelial cells (BAEC) were treated with oxidized-low density lipoproteins (oxLDL). OxLDL, but not LDL, increased ECE-1 protein content, mRNA expression and promoter activity. Our results demonstrate that ECE-1 increases in different atherosclerosis situations. Up-regulation of ECE-1 could contribute, at least partially, to the development of hypertension seen in apoE mice, because FR-901533 avoided it. Probably, atherosclerotic situations course with an increase of oxLDL, which is able to induce ECE-1 expression with the subsequent potential pathological effects.-Martinez-Miguel, P., V. Raoch, C. Zaragoza, J. M. Valdivielso, M. Rodriguez-Puyol, D. Rodriguez-Puyol, and S. Lopez-Ongil. Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins. J. Lipid Res. 2009. 50: 364-375.
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