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 atherosclerotic 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) 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. 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. [Copyright &y& Elsevier]