FIBRIN(OGEN) AND VON-WILLEBRAND-FACTOR DEPOSITION ARE ASSOCIATED WITHINTIMAL THICKENING AFTER BALLOON ANGIOPLASTY OF THE RABBIT CAROTID-ARTERY

The aim of the study was to assess the contribution of thrombus incorp oration into neointimal thickening in the rabbit carotid artery after deep vascular injury induced by balloon angioplasty compared with supe rficial vascular injury induced by a perivascular collar. Besides CD 3 1 (PECAM I), vimentin, alpha-smooth muscle actin, rabbit anti-macropha ge monoclonal antibody and proliferating cell nuclear antigen, fibrin( ogen) and von Willebrand factor (vWF) deposition was assessed immunohi stochemically. Angioplasty was performed in 47 rabbits and evaluated i mmediately (n=7), after 6 hours (n=4), and after 1 (n=7), 2 (n=9), or 3 (n=20) weeks. A collar was placed in 29 rabbits and evaluated immedi ately (n=5), after 6 hours (n=5), and after 1 (n=7), 2 (n=10), or 3 (n =2) weeks. After dilatation, the arteries were extensively denuded of endothelium, the internal elastic membrane was ruptured and blood-fill ed clefts were present in the media, pointing to deep vascular (type I II) injury. Six hours later, mural fibrin(ogen) thrombi were formed, s pecially at sites with severe damage. This fibrin(ogen) matrix became infiltrated by phagocytes and smooth muscle cells. A luminal cap cover ed by regenerating endothelium was formed, demonstrating increased imm unoreactivity to vWF. vWF was deposited in the extracellular neointima l spaces. Fibrin(ogen) thrombus deposition and incorporation appeared to be protracted phenomena for at least 2 weeks. After collar placemen t, minimal endothelial denudation was documented, pointing to fecal su perficial (type I) vascular injury. In subsequent weeks, neointimal th ickening was associated with vWF deposition but not with fibrin(ogen) thrombus incorporation. In conclusion, mural fibrin(ogen) thrombus for mation and incorporation contribute to neointima formation after deep vascular injury and seem to occur for several weeks after the initial insult.