期刊
CURRENT VASCULAR PHARMACOLOGY
卷 11, 期 5, 页码 768-776出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570161111311050014
关键词
Milk fat globule epidermal growth factor VIII; arterial remodeling; intervention
资金
- National Institute on Aging, National Institutes of Health
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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