EXPERIMENTAL STUDIES
Arterialization of human vein grafts is associated with tenascin-C expression
Kurt Wallner, MD*,
Chen Li, MD, PhD*,
Michael C. Fishbein, MD ,
Prediman K. Shah, MD, FACC* and
Behrooz G. Sharifi, PhD*
* Division of Anatomic Pathology, and Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
Department of Pathology, UCLA School of Medicine, Los Angeles, California, USA
Manuscript received September 23, 1998;
revised manuscript received April 9, 1999,
accepted May 16, 1999.
Reprint requests and correspondence: Dr. Behrooz G. Sharifi, Cedars-Sinai Medical Center, Davis Bldg. #1016, 8700 Beverly Blvd., Los Angeles, California 90048, USA
Sharifi{at}CSMC.edu
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 mRNA 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 adventitia and media of 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 detected in the neointima, but was strongly upregulated in the adventitia and media, 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, 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 a 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.
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Abbreviations and Acronyms
| | AEC | = amino-4-ethylcarbazolein N,N dimethylformamide | | CABG | = coronary artery bypass grafting | | ECM | = extracellular matrix | | SMC | = smooth muscle cells | | SVG | = saphenous vein grafts | | TN-C | = tenascin-C |
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