Angiotensin II via activation of type 1 receptor upregulates expression ofendoglin in human coronary artery endothelial cells

Transforming growth factor-beta1 and its subtype receptor endoglin are key components in angiogenesis. We explored the role of angiotensin (Ang) II in the expression of endoglin and the underlying intracellular signaling mech anism in human coronary artery endothelial cells. Incubation of cells with Ang II upregulated endoglin expression in a concentration- and time-depende nt manner (maximal effect with 10(-6) mol/L Ang II at 24 hours). The Ang II type 1 receptor blocker losartan, but not the type 2 receptor blocker PD 1 23,319, completely blocked the effect of Ang II. In parallel experiments, t he mitogen-activated protein kinase inhibitor PID 098,059 fully inhibited t he effect of Ang II on the expression of endoglin. Incubation of endothelia l cells with Ang II also increased the expression of transforming growth fa ctor-beta1 and -beta2 receptors and simultaneously decreased the levels of transforming growth factor-beta1. These effects of Ang II were also attenua ted by losartan. We propose that Ang II via its type 1 receptor activation modulates the expression of transforming growth factor-beta1 receptors in h uman coronary endothelial cells. The activation of mitogen-activated protei n kinase plays an important role in this process. These observations provid e a new clue regarding the regulatory effect of Ang II on vascular remodeli ng after injury.