Endothelin-1 Down-Regulates Expression of

Endothelin-1 (ET-1) is known as a potent stimulator of cell proliferation and as a vasoconstrictor. It is believed that ET-1 contributes to the development of arterial diseases such as atherosclerosis. In this study, we demonstrated the expression of tropoelastin and lysyl oxidase (LO) on gene levels as induced by ET-1 in cultured smooth muscle cells (SMCs). ET-1 stimulated cell proliferation in a dose–dependent manner, and the level of this proliferation increased about 1.3-fold at 100 nM of ET-1. ET-1 suppressed the tropoelastin protein synthesis in a dose–dependent and time-dependent manner. In addition, ET-1 dose–dependently suppressed the tropoelastin and LO mRNA expres-sion. The tropoelastin and LO mRNA levels decreased to about half and 4/5, respectively, at 100 nM of ET-1. The inhibition of elastin synthesis was completely prevented by BQ123, an endothelin receptor A (ETA) antagonist. These results indicate that ET-1 can modulate the tropoelastin and LO mRNA expression via an ETA receptor in cultured SMC and that the regulator for elastin expression may play an important role in elastogenesis and SMC proliferation during the development of atherosclerosis. Key words —– — elastin, lysyl oxidase, endothelin-1, smooth muscle cell, endothelin A recepto