Arterialization of human vein crafts is associated with tenascin-C expression

OBJECTIVES This study was performed to test the hypothesis that tenascin-C (TN-C), an extracellular matrix (ECM) protein with counteradhesive chemotac tic and vascular growth-promoting effects, is expressed in "arterialized" h uman saphenous vein grafts (SVGs). BACKGROUND Tenascin-C is expressed in the vessel wall after vascular injury in the experimental model, where it has been implicated in the formation o f neointima. Overexpression of TN-C has also been implicated in the develop ment and progression of pulmonary hypertension. Saphenous vein grafts are e xposed to hemodynamic stress when interposed in the arterial circulation an d mechanical stress upregulates expression of TN-C, whereas stress-relaxati on suppresses its synthesis. We hypothesized that the hemodynamic stress of increased arterial pressure could also induce TN-C expression in SVG. METHODS We examined the expression of TN-C protein and mRNA in normal vein and "arterialized" human SVG using immunohistochemistry and in situ hybridi zation, respectively. RESULTS TN-C protein was not detected in control human saphenous veins; how ever, it was uniformly and strongly expressed in the adventitia and media o f patent human Vein grafts, with minimal or no expression in the neointima (n = 27, 100%). In situ hybridization showed that TN-C mRNA was not detecte d in the neointima, but was strongly upregulated in the adventitia and medi a, corroborating immunostaining data (n = 10, 100%). Unlike patent SVG, TN- C was not expressed in the adventitia of occluded grafts, except for a low level of expression around the newly formed vessels in neointima (n = 5, 10 0%). Smooth muscle cell-specific staining demonstrated that the lack of exp ression of TN-C in occluded vein grafts is not due to the lack of presence of smooth muscle cells in the graft. CONCLUSIONS These findings suggest that placement of a venous graft in the arterial system leads to expression of TN-C, which may in turn facilitate g raft remodeling. Conversely, loss of flow and intravascular pressure, assoc iated with vein graft occlusion, is accompanied by disappearance of TN-C ex pression. CT Am Coil Cardiol 1999;34:871-5) (C) 1999 by the American Colleg e of Cardiology.