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. Methods and Results: Syrian golden hamster, was used for preparing the atheroscle- rotic models by the administration of a high cholesterol diet （HC）, treatment with the nitric oxide synthase inhibitor （Nω-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） were 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. Conclusion: ET-1（1-31） might play in a role of promoting atherosclerosis, and especially be involved in inflammatory mediation during the progression of atherosclerosis