Linking Gene Dynamics to Intimal Hyperplasia - A Predictive Model of Vein Graft Adaptation

Abstract The long term outcome of Coronary Artery Bypass Graft (CABG) surgery remains unsatisfactory to this day. Despite years of improvements in surgical techniques and therapies administered, re-occlusion of the graft is experienced in 10-12% of the cases within just few months (Motwani JC, 1998). We suggest that an efficient post-surgical therapy might be found at the genetic level. Accordingly, we propose a multiscale model that is able to replicate the healing of the graft and detail the level of impact of targeted clusters of genes on the graft’s healing. A key feature of our integrated model is its capability of linking the genetic, cellular and tissue levels with feedback bridges in such a way that every single variation from an equilibrium point is reflected on all the other elements, creating a highly organized loop. Once validated on experimental data, our model offers the possibility to test several gene therapies that aim to improve the patency of the graft lumen in advance. Being able to anticipate the outcome will speed up the development of an efficient therapy and may lead to prolonged life expectancy of the graft.