PMID- 18997155 OWN - NLM STAT- MEDLINE DCOM- 20090415 LR - 20210512 IS - 0022-2275 (Print) IS - 0022-2275 (Linking) VI - 50 IP - 3 DP - 2009 Mar TI - Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins. PG - 364-375 LID - S0022-2275(20)30880-4 [pii] LID - 10.1194/jlr.M800215-JLR200 [doi] AB - 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. FAU - Martinez-Miguel, Patricia AU - Martinez-Miguel P AD - P. Martinez-Miguel and V. Raoch contributed equally to the manuscript; Research Unit and Nephrology Section, Hospital Universitario Principe de Asturias, Alcala University, Madrid. FAU - Raoch, Viviana AU - Raoch V AD - P. Martinez-Miguel and V. Raoch contributed equally to the manuscript; Research Unit and Nephrology Section, Hospital Universitario Principe de Asturias, Alcala University, Madrid. FAU - Zaragoza, Carlos AU - Zaragoza C AD - Centro Nacional de Investigaciones Cardiovascular (CNIC), Madrid, Lerida, Spain. FAU - Valdivielso, Jose Manuel AU - Valdivielso JM AD - Hospital Universitario Arnau de Vilanova, Lerida, Spain. FAU - Rodriguez-Puyol, Manuel AU - Rodriguez-Puyol M AD - Physiology and Medicine Departments, Alcala University, Madrid. FAU - Rodriguez-Puyol, Diego AU - Rodriguez-Puyol D AD - D. Rodriguez-Puyol and S. Lopez-Ongil contributed equally to the manuscript; Research Unit and Nephrology Section, Hospital Universitario Principe de Asturias, Alcala University, Madrid; Physiology and Medicine Departments, Alcala University, Madrid. FAU - Lopez-Ongil, Susana AU - Lopez-Ongil S AD - D. Rodriguez-Puyol and S. Lopez-Ongil contributed equally to the manuscript; Research Unit and Nephrology Section, Hospital Universitario Principe de Asturias, Alcala University, Madrid. Electronic address: slopez.hupa@salud.madrid.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081107 PL - United States TA - J Lipid Res JT - Journal of lipid research JID - 0376606 RN - 0 (Apolipoproteins E) RN - 0 (Lipoproteins, LDL) RN - 0 (NF-kappa B) RN - 0 (OLR1 protein, human) RN - 0 (Olr1 protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (Scavenger Receptors, Class E) RN - 0 (oxidized low density lipoprotein) RN - 9007-49-2 (DNA) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.71 (ECE1 protein, human) RN - EC 3.4.24.71 (Ece1 protein, mouse) RN - EC 3.4.24.71 (Endothelin-Converting Enzymes) SB - IM MH - Aged MH - Animals MH - Apolipoproteins E/deficiency/genetics MH - Aspartic Acid Endopeptidases/genetics/*metabolism MH - Atherosclerosis/etiology/genetics/*metabolism/physiopathology MH - Base Sequence MH - Cattle MH - Cells, Cultured MH - DNA/genetics MH - Endothelial Cells/drug effects/metabolism MH - Endothelin-Converting Enzymes MH - Humans MH - Hypercholesterolemia/blood/enzymology MH - Lipoproteins, LDL/*metabolism/pharmacology MH - Male MH - Metalloendopeptidases/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Middle Aged MH - NF-kappa B/metabolism MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics/metabolism MH - Scavenger Receptors, Class E/blood/metabolism MH - Up-Regulation/drug effects EDAT- 2008/11/11 09:00 MHDA- 2009/04/16 09:00 CRDT- 2008/11/11 09:00 PHST- 2008/11/11 09:00 [pubmed] PHST- 2009/04/16 09:00 [medline] PHST- 2008/11/11 09:00 [entrez] AID - S0022-2275(20)30880-4 [pii] AID - 10.1194/jlr.M800215-JLR200 [doi] PST - ppublish SO - J Lipid Res. 2009 Mar;50(3):364-375. doi: 10.1194/jlr.M800215-JLR200. Epub 2008 Nov 7.