Overexpression of the focal adhesion kinase (p125 (FAK)) in the vascular smooth muscle cells of intimal hyperplasia

Purpose: The migration and proliferation of vascular smooth muscle cells (V SMCs) are important events in the development of intimal hyperplasia (IH). The focal adhesion kinase (FAK) gene encodes a protein tyrosine kinase (p12 5(FAK)) involved in signal transduction pathways used in cell adhesion, mot ility, and proliferation. Because alterations in these cellular processes a re thought to occur in VSMCs during IH, we studied FAK expression in health y arteries and veins in comparison with that in pathologic vessels containi ng IH. Methods: To determine p125(FAK) expression at the cellular level, we develo ped a monoclonal antibody that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections (5 mum) and analyzed the levels of FAR e xpression in human arteries arid veins. Specificity of monoclonal antibody 4.47 was demonstrated by means of immunofluorescence microscopy showing FAK -specific staining at focal adhesions of healthy human vascular smooth musc le cells (AoSMCs). By using immunohistochemistry techniques, we analyzed th e expression of p125(FAK) in 25 adult human vascular tissue samples from in dividual patients, which contained a histologically confirmed healthy arter y, vein, or IH. Results: FAK expression in healthy and pathologic human vascular tissue was localized predominantly within VSMC cytoplasm. In healthy human artery and vein, borderline FAR expression was detected in the media of seven of 17 v essels and undetectable in the remainder of specimens. However, in vessels containing IH, FAR was overexpressed in the pathologic VSMC populations at moderate-to-strong levels in eight of eight specimens. The levels of FAK ex pression were directly correlated with structures containing IH, and the re sults of FAR staining intensity and the percentage of positive cells in the se samples were significantly increased compared with normal vascular tissu e levels (P <.05, Student t test). Conclusion: These results provide the first evidence that FAK is overexpres sed in VSMCs involved in IH and suggest that FAK upregulation may be part o f a mechanism for migration and proliferation of VSMCs during this process. Furthermore, the dramatic upregulation of FAK in IH and the relative lack of expression in healthy vessels suggest that FAK, may be a rational target for controlling IH.