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Amyloidogenic medin induces endothelial dysfunction and vascular inflammation through the receptor for advanced glycation endproducts.


ABSTRACT:

Aims

Medin is a common amyloidogenic protein in humans that accumulates in arteries with advanced age and has been implicated in vascular degeneration. Medin's effect on endothelial function remains unknown. The aims are to assess medin's effects on human arteriole endothelial function and identify potential mechanisms underlying medin-induced vascular injury.

Methods and results

Ex vivo human adipose and leptomeningeal arterioles were exposed (1?h) to medin (0.1, 1, or 5 µM) without or with FPS-ZM1 [100 µM, receptor for advanced glycation endproducts (RAGE)-specific inhibitor] and endothelium-dependent function (acetylcholine dilator response) and endothelium-independent function (dilator response to nitric oxide donor diethylenetriamine NONOate) were compared with baseline control. Human umbilical vein endothelial cells were exposed to medin without or with FPS-ZM1 and oxidative and nitrative stress, cell viability, and pro-inflammatory signaling measures were obtained. Medin caused impaired endothelial function (vs. baseline response: -45.2?±?5.1 and -35.8?±?7.9% in adipose and leptomeningeal arterioles, respectively, each P?ConclusionsMedin causes human microvascular endothelial dysfunction through oxidative and nitrative stress and promotes pro-inflammatory signaling in endothelial cells. These effects appear to be mediated via RAGE. The findings represent a potential novel mechanism of vascular injury.

SUBMITTER: Migrino RQ 

PROVIDER: S-EPMC6676393 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Amyloidogenic medin induces endothelial dysfunction and vascular inflammation through the receptor for advanced glycation endproducts.

Migrino Raymond Q RQ   Davies Hannah A HA   Truran Seth S   Karamanova Nina N   Franco Daniel A DA   Beach Thomas G TG   Serrano Geidy E GE   Truong Danh D   Nikkhah Mehdi M   Madine Jillian J  

Cardiovascular research 20170901 11


<h4>Aims</h4>Medin is a common amyloidogenic protein in humans that accumulates in arteries with advanced age and has been implicated in vascular degeneration. Medin's effect on endothelial function remains unknown. The aims are to assess medin's effects on human arteriole endothelial function and identify potential mechanisms underlying medin-induced vascular injury.<h4>Methods and results</h4>Ex vivo human adipose and leptomeningeal arterioles were exposed (1 h) to medin (0.1, 1, or 5 µM) with  ...[more]

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