Up4A was discovered in 2005 as a novel endothelium-derived contractile factor,EDCF released from endothelial cells (Jankowski et al.Nat Med 11:223 2005).We further established that Up4A induced contraction of rat pulmonary arterial tissues.This action was found through activation ofa suramin-sensitive P2Y receptor (Gui et al.Am J Physiol 294:L733 2008).Importantly,we have found that high blood concentration of Up4A is correlated to high blood pressure in children and the development of neointima formation in carotid arteries (Jankowski et al.Arterioscler Thromb Vasc Biol 27:1776 2007).Our in vitro studies showed that Up4A stimulates the proliferation of huma vascular smooth muscle cells (SMCs).The mechanism involves P2Y receptor activation as well.More recently,using cultured human vascular SMCs,we demonstrated that intracellular signalling mechanism underlying Up4A-induced proliferation of SMCs involves activation of Erk1/2 and Erk1/2-dependent S6K pathways.Taken together,our research has reveled that Up4A is a potent vasoconstrictor and a mitogen for vascular SMCs,and could become the target of drug development to treat hypertension and other proliferative vascular diseases,including atherosclerosis and restenosis after angioplasty.