Mechanisms of neointima formation in renal transplant vasculopathy

PhD ceremony: Ms. M. Boersema, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Mechanisms of neointima formation in renal transplant vasculopathy

Promotor(s): prof. J.L. Hillebrands, prof. G.J. Navis

Faculty: Medical Sciences

In this thesis, we investigated the cellular and molecular mechanisms leading to neointima formation after renal transplantation in experimental and human studies. The neointima consists of smooth muscle cells, which produce extracellular matrix, intermingled with recipient-derived mononuclear cells. This intimal accumulation of cells and extracellular matrix will eventually lead to luminal stenosis and consequently ischemic graft failure. For the development of new therapies, it is important to know the origin of neointimal cells and the molecular mechanisms of neointima formation. This thesis shows that neointimal smooth muscle cells are mainly derived from the transplanted kidney. Further research showed that the phenotype of medial smooth muscle cells changes after transplantation from contractile to synthetic. Synthetic smooth muscle cell can produce extracellular matrix and have the ability to migrate. Therefore, medial smooth muscle cell are a possible source of neointimal smooth muscle cells.