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Milk Fat Globule Epidermal Growth Factor VIII Signaling in Arterial Wall Remodeling

[ Vol. 11 , Issue. 5 ]

Author(s):

Mingyi Wang, Hejia H. Wang and Edward G. Lakatta   Pages 768 - 776 ( 9 )

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.

Keywords:

Milk fat globule epidermal growth factor VIII, arterial remodeling, intervention.

Affiliation:

Laboratory of Cardiovascular Science, National Institute on Aging-National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.



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