Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half LIM domains 5 plays a key role for vein graft intimal hyperplasia

Intimal hyperplasia (IH) is the cause of vein graft stenosis or failure after bypass surgery. However, no therapeutic targets for the treatment of IH have been identified. We identified two previously unrecognized IH-inducing molecules, mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3) and four-and-a-half LIM domains 5 (FHL5), using gene expression profiling of human vein graft samples and demonstrated that MAPKAPK3 and FHL5 can activate cyclic adenosine monophosphate response-element binding protein (CREB) and a promising strategy for treating IH via gene transfer of KREB, a dominant-negative variant. Our study began with one patient, and we confirmed our findings on MAPKAPK3 and FHL5 expression using vein samples from eight other patients. We believe that these results will lead to new clinical approaches to IH.