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| Status |
Public on Dec 02, 2010 |
| Title |
Progerin Expression in Endothelial Cells Induces Endothelial Dysfunction |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Yap B, Kiely J, Stravrakis G, Zhang Y, Garcia-Cardena G, Gimbrone MA Jr |
| Citation missing |
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| |
| Submission date |
Dec 02, 2009 |
| Last update date |
Jan 27, 2016 |
| Contact name |
Belinda Yap |
| E-mail(s) |
byap@rics.bwh.harvard.edu
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| Phone |
617-525-4341
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| Fax |
617-525-4329
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| Organization name |
Brigham and Women's Hospital, Harvard Medical School
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| Department |
Pathology
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| Lab |
Center for Excellence in Vascular Biology
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| Street address |
77 Avenue Louis Pasteur, NRB 752
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL2986 |
ABI Human Genome Survey Microarray Version 2 |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA120945 |
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