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Review
. 2013 Sep;11(5):768-76.
doi: 10.2174/1570161111311050014.

Milk fat globule epidermal growth factor VIII signaling in arterial wall remodeling

Mingyi Wang  1 , Hejia H Wang, Edward G Lakatta
Affiliations
Review

Milk fat globule epidermal growth factor VIII signaling in arterial wall remodeling

Mingyi Wang et al. Curr Vasc Pharmacol. 2013 Sep.

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.

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Conflict of interest statement

Conflicts of Interest

None.

Figures

Figure 1
Figure 1
Schematic depicting the structure of MFG-E8. EGF: epidermal growth factor domain; C1 and C2: discoid domains or coagulation factor V or VIII-homologous domains. PT: proline/threonine-enrich motif.
Figure 2
Figure 2
MGF-E8 protein within the aortic wall in rats (A), monkeys (B), and humans (C). From Fu Z et al [14].
Figure 3
Figure 3
Diagram of a diverse role for MFG-E8 in vascular cells.
Figure 4
Figure 4
Diagram of multiple roles for microparticles in the arterial wall.
See this image and copyright information in PMC

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