Narrowing of the arteries is the underlying cause of several vascular diseases including coronary artery disease, peripheral artery disease, carotid artery stenosis, or the occlusion of a coronary artery bypass. An international team of investigators led by Sonja Schrepfer (Hamburg/Kiel/Lübeck) have now described for the first time in Nature DOI: 10.1038/nature13232 a new mechanism that plays a significant role in arterial narrowing. Injury to a blood vessel, for example during the placement of a stent, is followed by an inflammatory response. As a result, the smooth muscle cells in the arterial wall switch temporarily to a state which is characterized by rapid cell proliferation and reduced apoptosis. Although this state is only transient, it is responsible for the development of narrowing of the blood vessels. The researchers were able to identify a key mitochondrial protein whose inhibition counteracts arterial narrowing. This new mechanism has not only been described in cell culture and small animal models, it also appears to play an important role in preclinical large animal and humanized in vivo models. Basic research studies have thus identified a new target which may give rise to novel substances that can be applied in the clinical setting to prevent vascular narrowing. It is worth noting that inhibition of the mechanism described by the team of investigators does not prevent vascular re-endothelization - a process that is crucially important for vascular repair.
In addition to 15 scientists from the University Medical Center Hamburg Eppendorf (UKE), scientists from the USA (Stanford), Sweden (Stockholm), Spain (Salamanca) and Germany (Lübeck) contributed to this study. Plans are already underway to conduct clinical trials at UKE.