Osteoprotegerin and diabetic macroangiopathy

Osteoprotegerin (OPG) is a bone-related protein that is also present in the vasculature. Recent data suggest that it may play a special role in arterial disease among patients with diabetes. Diabetic macroangiopathy is characterized by a series of diffuse, non-atherosclerotic alterations that hypothetically increase the vulnerability of the vessel wall to atherogenic processes. One prominent feature of the macroangiopathy is linear media calcifications, which have been found to impose a strong risk of future cardiovascular events in epidemiological studies. The mechanisms behind the development of calcifications are unknown, but may be related to the occurrence of diffuse matrix alterations in the arterial wall in diabetes. Interestingly, we have recently observed that the amounts of OPG are increased in the tunica media in arterial tissue from diabetic patients. OPG has been linked to vascular calcifications in immunohistochemical analysis of atherosclerotic tissue and experimental studies on OPG knockout mice. Thus, it is possible that increased arterial OPG concentrations reflect an osteogenic transformation of the vasculature in patients with diabetes as an aspect of diabetic macroangiopathy. This review will evaluate data about OPG in the vasculature and focus on a possible role of OPG in the arterial wall in diabetes.