Development and Differentiation of Vascular Smooth Muscle

After a network of large and small endothelial channels suitable to conduct the nascent embryonic circulation has formed, the next step in vascular development is the assembly of a tunica media to provide mechanical support, prevent hemorrhage and rupture, and confer vasomotor and neurohumoral control of the circulation. Formation of the tunica media is a stepwise process involving recruitment and clustering of mesenchymal cells around endothelial vessels, activation of smooth muscle specific gene transcription, production of an elastin-and collagen-rich extracellular matrix, organization of smooth muscle cells (SMCs) into layers, and formation of an adventitia consisting of nerves, capillaries, fibroblasts, and connective tissue. Reciprocal signaling between endothelial cells and mesenchymal cells is critical for assembly of the tunica media, both to ensure endothelial cell survival and maturation and to stimulate mesenchymal cell differentiation and matrix production. The exchange of signals between endothelial cells and mesenchymal cells that is initiated during vascular development continues throughout life to ensure that changing target tissue demands for perfusion are coupled with corresponding adaptations in the structure and function of the tunica media.