Browsing by department "Haartman Institute, Transplantation Laboratory"

Chronic allograft nephropathy is still the major cause for loss of transplanted kidneys. A prominent feature is luminal narrowing of blood vessels due to proliferating and migrating smooth muscle cells (SMCs). The mechanism is much like that of atherosclerosis. We hypothesized that platelet derived growth factor (PDGF), vascular endothelial growth factor and epidermal growth factor play an important role in the process. This was based on the observation that drugs inhibiting these growth factors decreased luminal narrowing in a rat model. To test the hypothesis SMC were cultured in vitro. They were stimulated to proliferate with PDGF. After this, two growth factor inhibitors, sunitinib and erlotinib, were administered to the culture in three different doses. The results are clear: both sunitinib and erlotinib inhibit SMC proliferation in a dose dependent matter. If SMC proliferation and migration could be prevented, it could potentially result in a decrease of late allograft loss.