Arterial inflammation and remodeling, important sequellae of advancing age, are linked to the pathogenesis of
age-associated arterial diseases e.g. hypertension, atherosclerosis, and metabolic disorders. Recently, high-throughput
proteomic screening has identified milk fat globule epidermal growth factor VIII (MFG-E8) as a novel local biomarker for
aging arterial walls. Additional studies have shown that MFG-E8 is also an element of the arterial inflammatory signaling
network. The transcription, translation, and signaling levels of MFG-E8 are increased in aged, atherosclerotic,
hypertensive, and diabetic arterial walls in vivo as well as activated vascular smooth muscle cells (VSMC) and a subset of
macrophages in vitro. In VSMC, MFG-E8 increases proliferation and invasion as well as the secretion of inflammatory
molecules. In endothelial cells (EC), MFG-E8 facilitates apoptosis. In addition, MFG-E8 has been found to be an essential
component of the endothelial-derived microparticles that relay biosignals and modulate arterial wall phenotypes.
This review mainly focuses upon the landscape of MFG-E8 expression and signaling in adverse arterial remodeling. Recent
discoveries have suggested that MFG-E8 associated interventions are novel approaches for the retardation of the enhanced
rates of VSMC proliferation and EC apoptosis that accompany arterial wall inflammation and remodeling during
aging and age-associated arterial disease.