Local expression of bovine decorin by cell-mediated gene transfer reduces neointimal formation after balloon injury in rats

Decorin is an extracellular matrix (ECM) proteoglycan that may modify vascu lar smooth muscle cell (SMC) function by altering the response to growth fa ctors and the accumulation of ECM proteins during vascular injury. To inves tigate these possibilities in vivo, decorin was overexpressed at the site o f arterial injury by cell-mediated gene transfer. Fischer rat SMCs were tra nsduced in vitro with a retroviral construct that contained the bovine deco rin gene and were subsequently seeded into injured rat carotid arteries, A species-specific antibody to bovine decorin and polymerase chain reaction p rimers were used to detect bovine decorin and distinguish it from endogenou s rat decorin, Immunohistochemical and Northern analyses of rat carotid art eries revealed only low levels of rat decorin expression up to 8 weeks afte r balloon injury. However, after cell-mediated transfer of bovine decorin, strong expression of bovine decorin was verified by immunohistochemistry an d reverse transcriptase-polymerase chain reaction. Four weeks after injury, the intimal area in vessels seeded with bovine decorin-overexpressing SMCs was significantly reduced by 35+/-4% (mean+/-SEM, n=9; P<0.01). Decorin ov erexpression also induced a higher intimal nuclear density and decreased vo lume of ECM, Specifically, immunostaining for versican and fibronectin was markedly reduced. In contrast, immunostaining for collagen type I was incre ased,;and electron microscopy confirmed that collagen accumulation was alte red. Bromodeoxyuridine labeling indicated that intimal SMC proliferation wa s not affected by the expression of bovine decorin. In summary, we demonstr ate that gene transfer of the ECM proteoglycan, decorin, into the injured a rterial wall reduces intimal ECM volume and alters the composition of the E CM.