The role of the adventitia and perivascular tissue for the formation of intimal hyperplasia

Symptomatic atherosclerosis is commonly treated with balloon angioplasty or bypass surgery. About 30% of the interventions will re-narrow within a year due to restenosis and graft-stenosis. Thickening of the luminal layer, the intima, is an important component in these side-effects. Smooth muscle cells (SMCs) from the media have been regarded as responsible for the formation of the intimal hyperplasia. During the last decade the outermost vessel wall layer, the adventitia, and the perivascular tissue have been recognized as additional sources for intimal SMCs. The aim of this thesis was to investigate the role of the adventitia and the perivascular tissue in the formation of intimal hyperplasia. The specific aims were to investigate 1) if intimal hyperplasia can be inhibited from the adventitial side of a vessel, 2) if the adventitia and perivascular tissue can contribute with neointimal cells and 3) if the adventitia and perivascular tissue have a dynamic relation to other cellular sources in the formation of intimal hyperplasia. We used three different animal models for intimal hyperplasia: balloon injury to the rabbit carotid artery, implantation of vein grafts in mice and artificial grafts in pigs. Intimal hyperplasia following balloon injury could be inhibited from the adventitial side by placing a silicone collar around the treated artery. An external inhibition was also achieved in mice with a plastic shielding that isolated acellular vein grafts from the perivascular tissue.We could not find any cell migration from the adventitia / the perivascular tissue into the neointima in the rabbit carotid artery. However, in vascular grafts the perivascular tissue contributed with neointimal cells in both mouse and pig. A contribution from the blood was seen in rabbit and suggested in mouse and pig. In mouse, there was a dynamic relationship between different cellular sources. The donor vein and the perivascular tissue could fully compensate each other in the neointimal formation. In rabbit, we could not find this phenomenon. The media was the main cellular source and could not be fully compensated for by other sources.The results in this thesis show that different cellular sources, with a varying degree of compensatory abilities, contribute with neointimal cells. The cellular sources and their dynamic potential must be known and considered when inhibiting intimal hyperplasia following balloon injury and implantation of vascular grafts