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PUBLIC RELEASE DATE:
27-May-2014

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Contact: Corinne Williams
press_releases@the-jci.org
Journal of Clinical Investigation

JCI online ahead of print table of contents for May 27, 2014

Disturbed blood flow induces epigenetic alterations to promote atherosclerosis

Arterial hardening, also known as atherosclerosis, is the result of plaque buildup in the walls of arteries and over time can lead to cardiovascular complications, including heart attack, stroke, and peripheral vascular disease. Atherosclerotic plaques typically develop in arterial regions with disrupted blood flow. While blood flow disturbances are known to alter endothelial gene expression and function, it is not clear how altered blood flow induces these changes in endothelial cells. In this issue of the Journal of Clinical Investigation, Hanjoong Jo and colleagues at the Georgia Institute of Technology and Emory University present evidence that blood flow disturbances alter genome-wide methylation patterns in endothelial cells through the induction of the DNA methyltransferase DNMT. Long-term epigenetic changes induced within the arterial endothelium may further promote atherosclerosis, and genes that are altered in response to disturbed flow represent potential therapeutic targets for limiting plaque formation.

TITLE: Flow-dependent epigenetic DNA methylation regulates endothelial gene expression and atherosclerosis

AUTHOR CONTACT: Hanjoong Jo
Georgia Institute of Technology and Emory University, Atlanta, GA, USA
Phone: 1-404-712-9654; E-mail: hanjoong.jo@bme.gatech.edu

View this article at: http://www.jci.org/articles/view/74792


Protecting dopaminergic neurons from Parkinson's disease-associated degradation

A defining characteristic of Parkinson's disease (PD) is the prominent degeneration and loss of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc) region of the brain; however, it is not clear why this population of DA neurons is preferentially targeted in PD. In this issue of the Journal of Clinical Investigation, Huaibin Cai and colleagues at the National Institute on Aging identified a subpopulation of SNpc DA neurons lacking aldehyde dehydrogenase 1 (ALDH1A1) that are especially prone to degeneration and accumulation of cytotoxic levels of α-synuclein in a murine model of PD. Evaluation of PD patient and healthy brains revealed a reduction ALDH1A1 expression and reduced numbers of ALDH1A1-expressing DA neurons in the SNpc of PD patients. In PD mice, deletion of Aldh1a1 exacerbated both the loss of DA neurons and α-synuclein aggregation. Expression of ALDH1A1 in cultured DA neurons from PD mice enhanced cell survival, preventing caspase-mediated cell death. Together, the results from this study suggest that reduced ALDA1A1 expression in PD DA neurons makes this population vulnerable to α-synuclein-mediated degeneration.

TITLE: Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation

AUTHOR CONTACT: Huaibin Cai
National Institute on Aging, Bethesda, MD, USA
Phone: 301-402-8087; E-mail: caih@mail.nih.gov

View this article at: http://www.jci.org/articles/view/72176?key=c584826fe7a1ee622ffd


ALSO IN THIS ISSUE:

HEPATOLOGY

TITLE: Splicing regulator SLU7 is essential for maintaining liver homeostasis

AUTHOR CONTACT: Matías A. Ávila and Carmen Berasain
CIMA-University of Navarra, Pamplona, ESP
Phone: 34.948.194700; Fax: 34.948.194717; E-mail: maavila@unav.es (M.A. Ávila), cberasain@unav.es (C. Berasain)

View this article at: http://www.jci.org/articles/view/74382

ONCOLOGY

TITLE: Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

AUTHOR CONTACT: Markus Bredel
University of Alabama at Birmingham, Birmingham, AL, USA
Phone: 205-934-5199; E-mail: mbredel@uab.edu

View this article at: http://www.jci.org/articles/view/68836

TITLE: WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors

AUTHOR CONTACT: Randall Moon
University of Washington School of Medicine, Seattle, WA, USA
Phone: 206-543-1722; E-mail: rtmoon@u.washington.edu

Or

Andy J. Chien
University of Washington School of Medicine, Seattle, WA, USA
Phone: 206-616-4240; E-mail: andchien@uw.edu

View this article at: http://www.jci.org/articles/view/70156

TITLE: Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

AUTHOR CONTACT: Jean C. Shih
University of Southern California, Los Angeles, California, USA
Phone: 323.442.1441; Fax: 323.442.3229; E-mail: jcshih@usc.edu

Or

Leland W.K. Chung
Cedars-Sinai Medical Center, Los Angeles, California, USA
Phone: 310.423.7622; Fax: 310.423.8543; E-mail: leland.chung@cshs.org.

Or

Haiyen E. Zhau
Cedars-Sinai Medical Center, Los Angeles, California, USA
Phone: 310.423.8179; Fax: 310.423.8543; E-mail:haiyen.zhau@cshs.org.

View this article at: http://www.jci.org/articles/view/70982

TITLE: Four individually druggable MET hotspots mediate HGF-driven tumor progression

AUTHOR CONTACT: Paolo Michieli
Institute for Cancer Research and Treatment, Candiolo, Torino, UNK, ITA
Phone: +390119933219; Fax: +390119933225; E-mail: paolo.michieli@ircc.it

View this article at: http://www.jci.org/articles/view/72316

VASCULAR BIOLOGY

TITLE: β2-adrenergic agonists augment air pollution-induced IL-6 release and thrombosis

AUTHOR CONTACT: Gokhan Mutlu
The University of Chicago, Chicago, IL, USA
Phone: 773-702-1002; Fax: 773-702-6500; E-mail: g-mutlu@northwestern.edu

View this article at: http://www.jci.org/articles/view/75157

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