title: Milk fat globule epidermal growth factor VIII signaling in arterial wall remodeling.
abstract: 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.
authors.affiliation: Laboratory of Cardiovascular Science, National Institute on Aging-National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. mingyiw@grc.nia.nih.gov.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Wang
authors.forename: Hejia H
authors.initials: HH
authors.lastname: Wang
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D066292:Lipid Droplets; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D006017:Glycolipids; D006023:Glycoproteins; D008894:Milk Proteins; C110367:milk fat globule; D004815:Epidermal Growth Factor