Transforming growth factor-β in graft vessels: histology and immunohistochemistry

OBJECTIVES: The biological functions of transforming growth factor-β signaling that involves Smad proteins have not been previously investigated with respect to coronary artery bypass grafts. The aim of the present study was to observe the immunostaining of proteins that are related to this signaling pathway. METHODS: Fifteen remnants of coronary artery bypass grafts, including nine saphenous veins, three radial arteries and three mammary arteries, were collected from 12 patients who were undergoing coronary artery bypass. Hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining of transforming growth factor-β(1), type I receptor of transforming growth factor-β, Smad2/3, Smad4, and Smad7 were performed. RESULTS: The saphenous veins showed more severe intimal degeneration, more severe smooth muscle cell proliferation and more collagen deposition than the arterial grafts, as evidenced by hematoxylin and eosin and Masson's trichrome stainings. Immunohistochemical assays demonstrated that the majority of the transforming growth factor -β(1) signaling cytokines were primarily localized in the cytoplasm in the medial layers of all three types of grafts, whereas ectopic transforming growth factor-β(1), type I receptor of transforming growth factor-β, and Smad7 overexpressions in the interstices were observed particularly in the saphenous vein and radial arterial grafts. CONCLUSION: Enhanced transforming growth factor-β(1) signal transduction with medial smooth muscle cell proliferation and ectopic transforming growth factor-β(1), the presence of the type I receptor of transforming growth factor-β, and Smad7 overexpressions in the extracellular matrix may provide primary evidence for early or late graft failure.