Milk Fat Globule Epidermal Growth Factor VIII Fragment Medin in Age-Associated Arterial Adverse Remodeling and Arterial Disease

Abstract

Medin, a small 50-amino acid peptide, is an internal cleaved product from the second discoidin domain of milk fat globule epidermal growth factor VIII (MFG-E8) protein. Medin has been reported as the most common amylogenic protein in the upper part of the arterial system, including aortic, temporal, and cerebral arterial walls in the elderly. Medin has a high affinity to elastic fibers and is closely associated with arterial degenerative inflammation, elastic fiber fragmentation, calcification, and amyloidosis. In vitro, treating with the medin peptide promotes the inflammatory phenotypic shift of both endothelial cells and vascular smooth muscle cells. In vitro, ex vivo, and in vivo studies demonstrate that medin enhances the abundance of reactive oxygen species and reactive nitrogen species produced by both endothelial cells and vascular smooth muscle cells and promotes vascular endothelial dysfunction and arterial stiffening. Immunostaining and immunoblotting analyses of human samples indicate that the levels of medin are increased in the pathogenesis of aortic aneurysm/dissection, temporal arteritis, and cerebrovascular dementia. Thus, medin peptide could be targeted as a biomarker diagnostic tool or as a potential molecular approach to curbing the arterial degenerative inflammatory remodeling that accompanies aging and disease.

MFG-E8, A Novel Biomarker for Alzheimer’s Disease and Its Amyloidotic Feature

“…These results indicate that secreted MFG-E8, not amyloidotic form, is likely to have a protective role. It has been demonstrated that medin enhances various reactive oxygen species and reactive nitrogen species produced by both endothelial cells and vascular smooth muscle cells, which promotes vascular endothelial dysfunction and arterial stiffening [24]. On the other hand, it is obscure if the amyloidotic MFG-E8 has a role pathologically or physiologically.…”

Human cell-expressed tag-free rhMFG-E8 as an effective radiation mitigator

“…In addition, during aging, MFG-E8 could be cleaved into small 50-aa peptide named medin, which is a potent inflammatory molecule and very common amyloid protein observed in the old aortic, temporal, and cerebrovascular walls. However, it is still not known what, when, and how local proteinases cleaves MFG-E8 into medin in the arterial wall 44 . To explore the proinflammatory role of MFG-E8 in radiation mitigation, further studies are warranted in the future.…”