Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy

TLDR

The study examined endothelin‑1 effects on phosphoinositide hydrolysis, diacylglycerol formation, and myocardial cell hypertrophy in cultured neonatal rat ventricular cells, proposing endothelin‑1 as a paracrine regulator of cardiac growth. Hypertrophy was assessed by increases in cell size, myosin light chain‑2 assembly into contractile units, accumulation of contractile proteins, activation of immediate‑early genes, and induction of contractile and embryonic gene expression. Endothelin‑1 induced myocardial hypertrophy, ANF expression/release, cardiac‑specific gene transcription,.

Abstract

The present study examined the effects of endothelin-1 on phosphoinositide hydrolysis, diacylglycerol formation, and the induction of myocardial cell hypertrophy utilizing a well characterized cultured neonatal rat myocardial cell model. In this system, a hypertrophic response can be assessed by increases in myocardial cell size, an increase in the assembly of an individual contractile protein (myosin light chain-2) into organized contractile units, accumulation of contractile proteins, the activation of a program of immediate early gene expression, and the induction of genes encoding contractile and embryonic proteins (Iwaki, K., Sukhatme, V., Shubeita, H.E., Chien, K.R., (1990) J. Biol. Chem. 265, 13809-13817). Utilizing these criteria, the present study documents that stimulation with endothelin-1 can produce myocardial cell hypertrophy, induce the expression and release of ANF in ventricular cells, and can activate the transcription of cardiac-specific genes. In addition, endothelin-1 stimulates phosphoinositide hydrolysis and the accumulation of diacylglycerol. It is proposed that endothelin-1 stimulation may represent an important paracrine mechanism for the in vivo regulation of cardiac growth and hypertrophy.