Calcification by vascular cells is regulated by mechanical strain and MAPK signaling

Calcification in the cardiovascular system is a clinically significant problem believed to be actively mediated by vascular cells that acquire osteoblast-like functions. Vascular cells are mechanically responsive, and thus we hypothesized that calcification by vascular cells is regulated by mechanical strain, with involvement of mitogen-activated kinase (MAPK) intracellular signaling pathways. We tested our hypotheses by applying cyclic mechanical strain to calcifying vascular cells (CVCs) in vitro. We found accelerated expression of alkaline phosphatase, a marker of osteoblast differentiation, and increased mineralization by CVCs subjected to strain. When p38 MAPK activity was blocked biochemically, mineralization by the CVCs was inhibited, even when the cells were strained. These data suggest an important role for mechanical signals in regulation of vascular calcification, with necessary involvement of p38 MAPK signaling.