Der Effekt von Mycophenolatmofetil im humanen koronaren 3D-Leukozytenangriffsmodell
Weber, Christian Michael
LicenseStandard (Fassung vom 03.05.2003)
Despite great achievements coronary artery disease and restenosis after percutaneous coronary intervention are still an important topic concerning mortality and morbidity worldwide. A solution could deliver mycophenolate mofetil, an antiproliferative drug commonly used in transplant patients that was successfully tested in monoculture models of adhesion in concentrations that can be attained in vivo (50 µg/ml). We tested in a 3-dimensional co-culture model consisting of human coronary endothelial cells and human coronary smooth muscle cells the effect of mycophenolate on adhesion and migration of monocytes and proliferation of coronary smooth muscle cells. Monocyte adhesion was increased with mycophenolate between 8 % and 64 % depending on time of coincubation with monocytes of stimulated endothelial and muscle cells, while migration of monocytes was significantly reduced between 48 and 96 %. With mycophenolate pretreatment proliferation of smooth muscle cells after 24 hours of monocyte coincubation was significantly inhibited between 87 and 96 %. Most likely increased adhesion is due to impaired glycosilation of adhesion molecules, while reduced transmigration could be explained by the purine antagonism of mycophenolate. Proliferation is - in conjunction with the antiproliferative effect of mycophenolate (inhibition of inosine monophosphate dehydrogenase) - reduced highly significantly as expected. These results warrant further organ culture studies and clinical trials of mycophenolate in restenosis and native atherosclerosis.
Subject HeadingsAdhäsion [GND]
Mycophenolate mofetil [MeSH]