Increases of vascular endothelin-converting enzyme activity and endothelin-1 level on atherosclerotic lesions in hyperlipidemic rabbits.
The aim of this study was to investigate vascular endothelin-converting enzyme activity and the tissue level of endothelin-1 in the aorta related to atherosclerotic lesions in high cholesterol diet-fed rabbits. Rabbits were fed two atherogenic diets, 0.5% and 1.5% cholesterol, and a normal diet for 16 weeks. Vascular endothelin-converting enzyme activity in the aortic arch and thoracic aorta was significantly increased (2.0-4.4 times) by the atherogenic diet as compared with the normal diet group as well as the levels of lipids and lipid peroxide in plasma were significantly increased. Tissue endothelin-1 levels in both aortas were also elevated (2.3-6.8 times), corresponding well to the increased tissue enzyme activity. In contrast, plasma endothelin-1 levels increased only in the 1.5% cholesterol diet group (2.7 times). These results indicate that the endothelin-converting enzyme activity and the corresponding endothelin-1 level in the vascular walls increase in association with the development of atherosclerotic lesions.
Mitani
H
H
Takarazuka Research Institute, Novartis Pharma, 10-66 Miyuki-cho, Takarazuka, Japan. hironobu.mitani@pharma.novartis.com
Takimoto
M
M
Bandoh
T
T
Kimura
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001808:Blood Vessels / Q000201:enzymology*; D019332:Endothelin-1 / Q000032:analysis* / Q000097:blood; D000072396:Endothelin-Converting Enzymes; D006949:Hyperlipidemias / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008054:Lipid Peroxides / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008666:Metalloendopeptidases; D018384:Oxidative Stress; D011817:Rabbits
D019332:Endothelin-1; D007527:Isoenzymes; D008054:Lipid Peroxides; D008055:Lipids; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes