Arterialization of human vein grafts 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 chemotactic and vascular growth-promoting effects, is expressed in “arterialized” human 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 of neointima. Overexpression of TN-C has also been implicated in the development and progression of pulmonary hypertension. Saphenous vein grafts are exposed to hemodynamic stress when interposed in the arterial circulation and mechanical stress upregulates expression of TN-C, whereas stress-relaxation 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 mRN in normal vein and “arterialized” human SVG using immunohistochemistry and in situ hybridization, respectively. RESULTS TN-C protein was not detected in control human saphenous veins; however, it was uniformly and strongly expressed in the adventiti and medi of patent human vein grafts, with minimal or no expression in the neointim (n = 27, 100%). In situ hybridization showed that TN-C mRN was not detected in the neointima, but was strongly upregulated in the adventiti and media, corroborating immunostaining dat (n = 10, 100%). Unlike patent SVG, TN-C was not expressed in the adventiti of occluded grafts, except for low level of expression around the newly formed vessels in neointim (n = 5, 100%). Smooth muscle cell-specific staining demonstrated that the lack of expression 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 venous graft in the arterial system leads to expression of TN-C, which may in turn facilitate graft remodeling. Conversely, loss of flow and intravascular pressure, associated with vein graft occlusion, is accompanied by disappearance of TN-C expression.