Introduction: The focal adhesion protein zyxin participates in the organization of the cytoskeleton. However, the real function of zyxin is not known. In this study we have analyzed its role in vascular tone regulation and pressure-induced gene expression.

Methods: Femoral arteries freshly isolated from zyxin-null and wild type C57/BL6 mice were isolated and subjected to defined perfusion conditions in a pressure myograph with real time diameter measurement. Primary human endothelial cells (EC) were cultured on flexible membranes and subjected to cyclic strain in a computer-assisted device. Analytical standard procedures such as real time RT-PCR, Western blot and (immuno-)histochemisty were used.

Results: In response to increases in wall tension, zyxin translocates to the nucleus and mediates stretch-induced gene expression. Zyxin-deficient arteries respond to prolonged increases in pressure with a perpendicular rearrangement of medial smooth muscle cells. This adaptive alignment along the pressure gradient explains the inability of zyxin-deficient vessels to contract properly in response to vasoactive compounds such as epinephrine, ACh or ET-1.

Conclusion: In vascular cells, zyxin has a dual role as an organizer of the force-producing machinery and as a mechanotransducer upon mechanical overload.