Alternative splicing of endothelial fibronectin is induced by disturbed hemodynamics and protects against hemorrhage of the vessel wall.

ABSTRACT:

Objective

Abnormally low-flow conditions, sensed by the arterial endothelium, promote aneurysm rupture. Fibronectin (FN) is among the most abundant extracellular matrix proteins and is strongly upregulated in human aneurysms, suggesting a possible role in disease progression. Altered FN splicing can result in the inclusion of EIIIA and EIIIB exons, generally not expressed in adult tissues. We sought to explore the regulation of FN and its splicing and their possible roles in the vascular response to disturbed flow.

Approach and results

We induced low and reversing flow in mice by partial carotid ligation and assayed FN splicing in an endothelium-enriched intimal preparation. Inclusion of EIIIA and EIIIB was increased as early as 48 hours, with negligible increases in total F

SUBMITTER: Murphy PA 

PROVIDER: S-EPMC4140979 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature