Diabetes and vascular calcification

Abstract

Vascular calcification had been accepted as a passive, degenerative process, but recent findings suggested that it is actively regulated like osteogenesis. In addition, vascular calcification is roughly classified into two types: intimal arterial calcification (IAC) and medial arterial calcification (MAC). IAC is usually associated with atherosclerosis, whereas MAC is often associated with aging, diabetes, and chronic kidney disease. Although MAC does not directly cause stenotic or occlusive lesions, it may exacerbate arterial stiffness with significant hemodynamic changes, resulting in cardiovascular mortality. Transdifferentiation of vascular smooth muscle cells (VSMCs) and changes in extracellular matrix (ECM), which are mainly due to elastin degradation, are involved in the onset and progression of MAC. In particular, runt-related transcription factor 2 (Runx2) seems to play a critical role in the transformation of VSMCs from a vascular contractile phenotype into an osteoblast-like phenotype. The presence of diabetes accelerates both VSMC transdifferentiation through the upregulation of Runx2 and ECM changes by metalloproteinase-induced elastin degradation. Fetuin-A can act as not only an inducer of insulin resistance but also as an inhibitor of ectopic calcification through the formation of calciprotein particles (CPPs). Recently, it has been hypothesized that overproduction of CPPs could cause vascular damage, including vascular calcification. Since fetuin-A is involved in both diabetes and vascular calcification, precise investigation of CPPs may give new insights in this field.