Endothelin-1(1-31) levels are increased in atherosclerotic lesions of the thoracic aorta of hypercholesterolemic hamsters.
OBJECTIVE
The novel vaso-constricting 31-amino acid-length endothelin-1 [ET-1(1-31)] is selectively produced by human mast cell chymase via its action on big ET-1. However, the pathological role of ET-1(1-31) in atherosclerosis remains unclear. The aim of this study was to clarify vasoconstrictive response and expression of ET-1(1-31) in atherosclerotic aorta.


RESULTS
Syrian golden hamster, was used for preparing the atherosclerotic models by the administration of a high cholesterol diet (HC), treatment with the nitric oxide synthase inhibitor (Nomega-nitro-L-arginine methylester, L-NAME) alone, or both (HC and L-NAME) for 40 weeks. Early atherosclerosis was observed in the case of HC or L-NAME alone treatments respectively and severe atherosclerosis was observed in the case of combined HC and L-NAME treatment. Vasoconstriction induced by ET-1(1-31) was not altered by the atherosclerotic changes, but the expression pattern of ET-1(1-31) was different at each stage of the atherosclerotic aorta. ET-1(1-31) was observed rarely in normal aortas or in early atherosclerotic lesions, but ET-1(1-31) expression was dramatically increased in aortic neointima and adventitia in a state of atherosclerosis with severe inflammation.


CONCLUSIONS
ET-1(1-31) might play in a role of promoting atherosclerosis, and especially be involved in inflammatory mediation during the progression of atherosclerosis.
Mawatari
Kazuaki
K
Department of Nutrition, School of Medicine, Tokushima University, Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. mawatari@nutr.med.tokushima-u.ac.jp
Kakui
Sae
S
Harada
Nagakatsu
N
Ohnishi
Takamasa
T
Niwa
Yasuharu
Y
Okada
Kazuko
K
Takahashi
Akira
A
Izumi
Keisuke
K
Nakaya
Yutaka
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D006224:Cricetinae; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000031:analogs & derivatives* / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000502:physiology*
D019332:Endothelin-1; D010446:Peptide Fragments; D014280:Triglycerides; C114932:endothelin-1 (1-31); D002784:Cholesterol