Endothelin-1 down-regulates expression of tropoelastin and lysyl oxidase mRNA in cultured chick aortic smooth muscle cells

Abstract

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 expression. 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 (ET A) antagonist. These results indicate that ET-1 can modulate the tropoelastin and LO mRNA expression via an ET A 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.