Notch signaling governs phenotypic modulation of smooth muscle cells.

A feature of vascular smooth muscle cells is their unique ability to exist in multiple phenotypes permitting a broad range of functions that include contraction, proliferation, or synthesis and secretion of extracellular matrix. Although it is known that these phenotypes can be overlapping, the mechanisms that regulate phenotypic modulation are still unclear. Given that endothelial cells are known to convey signals to smooth muscle cells that govern their activities within the vasculature; we sought to better define how endothelial cells regulate phenotypic changes of smooth muscle cells in coculture conditions. Using human aortic smooth muscle cells, we show that endothelial cells promote an increase in a differentiated/contractile phenotype while decreasing proliferation. Analysis of the synthetic phenotype demonstrates that endothelial cells also increase collagen synthesis and secretion. Characterization of pathways important for these endothelial cell-dependent phenotypes reveal that Notch signaling plays an important role in the establishment of these smooth muscle properties. These data highlight the ability of endothelial cells to control phenotypic modulation in a unique and previously undefined manner.