Ke. Allen et al., HUMAN VENOUS ENDOTHELIUM CAN PROMOTE INTIMAL HYPERPLASIA IN A PARACRINE MANNER, Journal of vascular surgery, 19(4), 1994, pp. 577-584
Purpose: Vein graft stenoses resulting from the development of intimal
hyperplasia are the major cause of graft failure in the first postope
rative year. This study uses an organ culture of human saphenous vein
to model vein graft intimal hyperplasia and assess the involvement of
the endothelium in its development. Methods: Organ cultures of sapheno
us vein were established comprised of intact vein, vein denuded of end
othelium, or cocultures of intact plus denuded vein for 14 days in ser
um-supplemented medium. At the end of the culture period, veins were p
rocessed and sections prepared for immunostaining with monoclonal alph
a-smooth muscle actin, Millers elastin, QB END.10, and bromodeoxyuridi
ne. Results: After culture, a cellular neointima developed in the inta
ct veins that was significantly thicker than in those denuded of endot
helium (24.5 vs 2.5 mu m; p = 0.0001). Denuded veins in coculture with
intact veins developed a thicker neointima than did denuded veins alo
ne (12 vs 0 mu m; p = 0.01) but less than that of intact veins (12 vs
28 mu m; p < 0.01). Proliferation indexes followed the same trend (i.e
., intimal smooth muscle cell proliferation was greatest in intact and
least in denuded veins). Conclusion: The endothelium can promote neoi
ntimal formation in cultured human saphenous vein through a paracrine
action on the vascular smooth muscle cell.