The relationship between local renin-angiotensin system and intimal proliferation in an organ culture of human saphenous veins

Abstract

Local renin-angiotensin system (RAS) is implicated in development of intimal hyperplasia after vein bypass grafting, but little is known about the local angiotensin-converting enzyme (ACE) activity and the local responses of angiotensin II (AngII) in vein graft physiology. An organ culture of human saphenous vein was used as a model of vein graft intimal hyperplasia, and the role of local RAS in the development of neointimal proliferation was studied. Segments of saphenous veins were cultured for 14 days. One group was set as control, another two were cultured in medium with captopril, an ACE inhibitor and losartan, an Ang II receptor antagonist, respectively. All specimens were frozen in liquid nitrogen for ACE activity, histology, and immunohistochemistry studies. The concentration of ACE increased 37% in cultured veins to preculture veins. Immunohistochemical localization identified ACE in the endothelial layer of preculture veins and cultured veins, but at a greater density in the intimal hyperplasia of cultured veins. Captopril and losartan significantly reduced neointimal thickness by 49% and 34%, respectively. These data demonstrate that a positive relationship exist between local RAS and intimal proliferation. The use of ACE inhibitors and Ang II receptor antagonists have clinical significance in the prevention and treatment of vein graft disease.