Hl. Ding et al., Adenovirus-mediated expression of a truncated PDGF beta receptor inhibits thrombosis and neointima formation in an avian arterial injury model, THROMB HAEM, 86(3), 2001, pp. 914-922
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.