Endothelin stimulates c‐fos and c‐myc expression and proliferation of vascular smooth muscle cells

Abstract

Recently, a potent vasoconstrictor peptide, endothelin (EDT), was isolated from vascular endothelial cells. We examined its effect on rat vascular smooth muscle cells (VSMCs). EDT induced the elevation of intracellular calcium, which was dependent on extracellular calcium and inhibited by a calcium-channel antagonist in a competitive manner. EDT caused a rapid and transient increase in the c-fos and c-myc mRNA levels and stimulated the DNA synthesis of VSMCs in a dose-dependent manner. This effect of EDT on the proliferation of VSMCs might be related to the development of atherosclerosis.

Endothelin receptors in the human coronary artery, ventricle and atrium

“…In the heart, endothelin has been reported to elicit both positive inotropic (Moravec et al 1989;Kitayoshi et al 1989;Takanashi and Endoh 1991) and chronotropic (Ishikawa et al 1989) effects. Furthermore, endothelin induced mitogenesis of vascular smooth muscle cells (Komuro et al 1988;Ohlstein et al 1992) and hypertrophy of myocardial cells (Shubeita et al 1990) indicating that endothelin may play a role in the development of atherosclerosis and cardiac hypertrophy.…”

Formation of endothelin by cultured airway epithelial cells

“…It also promotes the release of prostaglandins from isolated lungs [3], endothelium-derived relaxing factor from blood vessels [3] and atrial natriuretic peptide from atrial myocytes [4] but inhibits the release of renin from isolated glomeruli [5]. In addition it stimulates the proliferation of vascular smooth muscle [6]. Two other forms of endothelin have now been characterised.…”

Calcium mobilization and Na+/H+ antiport activation by endothelin in human skin fibroblasts

“…ET-l mediated increases in Ca?' may result from activation of voltage-sensitive Ca2+ channels, as many of the observed responses are dihydropyridinesensitive and dependent on extracellular Ca2+ [1, 3,10,11]. However, in VSMC ET-l also increases inositol phosphates in concert with a rise in Car" [2,5,12,13], indicating Ca2+ mobilization from intracellular stores.…”

“…These include ET-l, which stimulates VSMC proliferation, DNA synthesis, and the induction of c-fos and c-myc mRNAs [3,4]. Since ET-l elicits growth-related responses in VSMCs, we investigated its action in an undifferentiated cell, the human skin fibroblast.…”