Adenovirus-mediated expression of a truncated PDGF beta receptor inhibits thrombosis and neointima formation in an avian arterial injury model

Platelet-derived growth factor (PDGF) is a major mediator of neointima form ation after arterial injury. We constructed a recombinant adenovirus, Ad/PD GFtr, that expresses the soluble extracellular domain of the murine PDGF be ta receptor (PDGFtr). The expressed PDGFtr was appropriately glycosylated a nd secreted by chicken vascular smooth muscle cells (SMCs) in vitro. The ex pressed PDGFtr inhibited human PDGF-BB induced receptor autophosphorylation , and also inhibited PDGF-BB induced cell proliferation without affecting P DGF-AA induced mitogenesis. In vivo transduction of balloon-injured rooster femoral arteries with Ad/PDGFtr resulted in expression and secretion of th e glycosylated PDGFtr. The expressed PDGFtr significantly inhibited neointi ma formation compared with controls. Neointima-associated thrombus was sign ificantly reduced in Ad/PDGFtr transduced arteries compared with controls. Thus, in addition to impacting on SMC proliferation and migration, PDGF-BB plays a role in thrombus formation in response to arterial injury. Growth f actor inhibition by localized gene delivery constitutes a powerful approach to intervene in the molecular pathways involved in vascular disease.