Abstract

Rationale: Medial vascular calcification (MAC) has been shown to be an active, cell-mediated process. Although several factors have been shown to promote vascular calcification including diabetes and kidney disease, a more complete understanding of the molecular mechanisms underlying the pathogenesis of this disease is needed.

Objective: To find out earliest markers in elastin mediated vascular smooth muscle cell calcification.

Methods and results: We provide evidence that the extracellular matrix protein, periostin, is strongly upregulated during in vitro and in vivo vascular smooth muscle cell calcification. RT-RCR and Western analyses demonstrate that upon stimulation with elastin peptides, rat aortic smooth muscle cells (RASMCs) exhibit a time-dependent increase in periostin expression, which is synergistically enhanced by the addition of transforming growth factor (TGF-β1). This increase was significantly attenuated by administering either lactose, an elastin-laminin receptor (ELR) antagonist, or the TGF-β1 receptor antagonist SB431542. As elastin peptides and TGF-β1 have been shown to contribute to RASMC calcification, the potential role of periostin in promoting RASMC calcification was further evaluated. Inhibition of periostin blocked RASMC calcification, whereas overexpression promoted calcification. This periostin-dependent calcification occurs, in part, through the regulation of osteogenic genes: alkaline phosphatase (ALP) and core binding factor 1 (Runx2/Cbfa-1). These data were further corroborated in a rat model of aortic calcific disease whereby periostin expression was confined to the calcified abdominal aorta.

Conclusions: Our results demonstrate that periostin is a potent osteogenic molecule in vascular smooth muscle cells and may play a significant role in mediating vascular calcification.

Keywords: Arteriosclerosis, medial arterial calcification, smooth muscle cells, osteogenesis, calcific disease, elastocalcinosis