Insulin-like growth factor induces up-regulation of AT1-receptor gene expression in vascular smooth muscle cells

Background Insulin-like growth factor-1 (IGF-1), as well as AT 1 -receptor activation, plays a central role in growth processes of cardiac and vascular cells. In order to assess relevant interactions of both systems, the effect of IGF-1 on AT 1 -receptor expression was evaluated in vascular smooth muscle cells. Methods and results Incubation of cultured vascular smooth muscle cells (VSMC) with IGF-1 led to a dose- and time-dependent up-regulation of AT 1 -receptor mRNA, as measured by Northern hybridisations. The maximal AT 1 -receptor overexpression of 201±70% of control levels was reached after a 24-hour incubation with 100 ng/ml IGF-1. Consequently, AT 1 -receptor protein expression was increased to 231±35% of control levels. Experiments under transcriptional blockade showed that AT 1 -receptor mRNA stability was not altered by IGF-1, suggesting that transcriptional mechanisms may be involved in IGF-1-induced AT 1 -receptor regulation. Preincubation with various pharmacological inhibitors revealed that IGF-1 up-regulated AT 1 -receptor expression via activation of p42/44 MAP kinase, whereas tyrosine phosphorylation and PI-3 kinase seemed not to participate in this regulative pathway. Conclusions IGF-1-induced up-regulation of the AT 1 -receptor may be an important interaction by which cellular growth is modulated in the heart as well as in the vasculature. This may have implications for the treatment regimen of patients suffering from hypertension, cardiac hypertrophy, and coronary heart disease.