In a collaborative study, mainly between Munich (Thorsten Kessler and Heribert Schunkert) and colleagues from the Department of Physiology and Pathophysiology in Beijing (Lu Zhang and Wei Kong), as well as Cor de Wit and Kjestine Schmidt from the University of Lübeck, members of the IIEG (Zouhair Aherrahrou as shared senior author and Jeanette Erdmann) have identified a novel mechanism by which ADAMTS-7 affects neointima formation.
ADAMTS-7, a hitherto rather unknown gene, had been found to be genome-wide significantly associated with coronary artery disease (CAD) by CARDIoGRAM, a consortium lead by Heribert Schunkert, Nilesh Samani and Jeanette Erdmann. However, the mechanisms that link ADAMTS-7 and CAD risk remained elusive.
Here, by employing transgenic mice we now revealed that ADAMTS-7 plays a pivotal role in vascular remodelling. After vascular injuryAdamts7-/- mice were resistant to neointima formation. Thus, inhibition of ADAMTS-7 might represent a promising therapeutic strategy for the prevention of restenosis after PCI. Moreover, Adamts7-/- mice displayed accelerated re-endothelialisation. As drug-eluting stents designed to reduce restenosis rates may actually retard re-endothelialisation – and thereby provoke stent thrombosis – the finding that ADAMTS-7 affects both processes may be of interest. In fact, inhibition of ADAMTS-7 may solve two problems at once, i.e. decrease restenosis and augment re-endothelialisation. Furthermore, the identification of thrombospondin-1 as an ADAMTS-7 target on one hand and as a modulator of vascular remodelling on the other hand might lead to the elucidation of further druggable downstream targets.