Dataset Information


Progerin Expression in Endothelial Cells Induces Endothelial Dysfunction

ABSTRACT: Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, genetic premature aging disorder associated with severe atherosclerosis, often resulting in fatal heart attacks and strokes. Progerin, the mutant protein in HGPS, also is expressed in healthy individuals and may play a role in the development of atherosclerosis during physiologic aging. Here, we provide evidence for a primary involvement of vascular endothelium in the pathogenesis of accelerated atherosclerosis in HGPS. Expression of progerin in cultured human endothelial cells induces a dysfunctional phenotype, manifested by activation of multiple pro-inflammatory, pro-atherogenic genes. In particular, our data implicate endothelial-derived interleukin-1 (IL-1) as a key mediator of a pro-inflammatory vascular phenotype. Endothelial activation also is detectable in a mouse model of HGPS, and appears to be conveyed to neighboring vascular cells via autocrine and paracrine signaling. These new mechanistic insights into the vascular pathobiology of HGPS may have therapeutic implications for this disease. Genome-wide transcriptional profiling was carried out to assess functional phenotypic changes in endothelial cells (EC) as a result of progerin expression. Cultured EC were infected with an adenovirus expressing progerin (Ad-Progerin), and as a control, an adenovirus that did not express any construct (Ad-Null). Experiments were preformed with three different EC cultures.

ORGANISM(S): Homo sapiens  

SUBMITTER: Belinda Yap   Guillermo Garcia-Cardena  Michael A Gimbrone Jr  Yuzhi Zhang  George Stravrakis  Jeanne-Marie Kiely 

PROVIDER: E-GEOD-19270 | ArrayExpress | 2010-12-02



Similar Datasets

2010-12-02 | GSE19270 | GEO
2011-03-14 | GSE24487 | GEO
2011-03-14 | E-GEOD-24487 | ArrayExpress
2013-09-22 | E-GEOD-47553 | ArrayExpress
2010-12-23 | GSE26093 | GEO
2010-12-23 | E-GEOD-26093 | ArrayExpress
| GSE101126 | GEO
2008-02-09 | GSE10123 | GEO
| GSE90982 | GEO
2012-01-13 | GSE32609 | GEO