The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia.JEis a platelet-derived growth factor (PDGF)-inducible “early” gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report thatJEmRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation ofJEmRNA in cultured VSMCs is accompanied by a marked increase in the secretion ofJEprotein. The elevation ofJEmRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, α-thrombin, and epidermal growth factor fail to increaseJEmRNA levels. In contrast to 3T3 fibroblasts, the accumulation ofJEmRNA in VSMCs in response to PDGF is predominantly due to an increase inJEmRNA stability. The accumulation ofJEmRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+mobilization, Na+-H+exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production ofJE, a potent monocyte chemoattractant. Finally, our data suggest thatJEmay be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded byJE.