Outside-In Signaling by Adventitial Fibroblasts

ot long ago, the blood vessel's adventitial layer was considered nondescript connective tissue comprised of fibroblasts and perivascular nerves.Several observations over the past 20 years have changed this misconception.The overexpression of endothelial nitric oxide synthase in adventitial fibroblasts rescued agonist-mediated vasodilation in arteries without endothelium and reactive oxygen species generated in the adventitial layer inactivated endothelium-derived nitric oxide.1,2 These data provided direct evidence that substances released from the adventitia could modify vascular function.The adventitia is now recognized as the most complex layer of the vessel wall, comprised not only of fibroblasts and nerves but of dynamic interactions between inflammatory cells, microvessels, lymphatics, and distinct subpopulations of progenitor cells.