Donate Help Contact The AHA Sign In Home
American Heart Association
Stroke
Search: search_blue_button Advanced Search
Published Online
on October 7, 2004

Stroke. 2004
Published online before print October 7, 2004, doi: 10.1161/01.STR.0000143216.85349.9e
A more recent version of this article appeared on November 1, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
35/11_suppl_1/2687    most recent
01.STR.0000143216.85349.9ev1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ratan, R. R.
Right arrow Articles by Chavez, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ratan, R. R.
Right arrow Articles by Chavez, J.
Related Collections
Right arrow Acute coronary syndromes

Submitted on July 12, 2004
Accepted on August 5, 2004

Translation of Ischemic Preconditioning to the Patient. Prolyl Hydroxylase Inhibition and Hypoxia Inducible Factor-1 as Novel Targets for Stroke Therapy

Rajiv R. Ratan MD, PhD*; Ambreena Siddiq PhD; Leila Aminova PhD; Philipp S. Lange MD; Brett Langley PhD; Issam Ayoub MD; JoAnn Gensert PhD; and Juan Chavez PhD

From the Department of Neurology and Neuroscience, Burke/Cornell Medical Research Institute, Weill Medical College of Cornell, White Plains, NY.

* To whom correspondence should be addressed. E-mail: rratan{at}caregroup.harvard.edu.

Abstract--Effective therapies for stroke must interdict multiple parallel and sequential pathophysiological events. A paradigm which offers insight into multivalent but thoughtfully coordinated protective programs is ischemic preconditioning. A central hypothesis of our group and others is that pharmacological agents that activate programs of gene expression normally induced by ischemic preconditioning will be effective agents for the prevention and treatment of stroke. Inhibitors of a class of enzymes, the hypoxia inducible factor-1 (HIF-1) prolyl hydroxylases stabilize the transcriptional activator HIF-1 and activate target genes involved in compensation for ischemia, including erythropoeitin (Epo) and vascular endothelial growth factor (VEGF). Here, we review evidence suggesting that the HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that pharmacological inhibitors of these enzymes are viable targets for stroke therapy.


Key words: acute care • hypoxia • ischemia • stroke • transcription




This article has been cited by other articles:


Home page
J. Biol. Chem.Home page
D. W. Lee, S. Rajagopalan, A. Siddiq, R. Gwiazda, L. Yang, M. F. Beal, R. R. Ratan, and J. K. Andersen
Inhibition of Prolyl Hydroxylase Protects against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Neurotoxicity: MODEL FOR THE POTENTIAL INVOLVEMENT OF THE HYPOXIA-INDUCIBLE FACTOR PATHWAY IN PARKINSON DISEASE
J. Biol. Chem., October 16, 2009; 284(42): 29065 - 29076.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
B. Langley, C. Brochier, and M. A. Rivieccio
Targeting Histone Deacetylases as a Multifaceted Approach to Treat the Diverse Outcomes of Stroke
Stroke, August 1, 2009; 40(8): 2899 - 2905.
[Abstract] [Full Text] [PDF]


Home page
StrokeHome page
R. R. Ratan and M. Noble
Novel Multi-Modal Strategies to Promote Brain and Spinal Cord Injury Recovery
Stroke, March 1, 2009; 40(3_suppl_1): S130 - S132.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
Y. A. Minamishima, J. Moslehi, N. Bardeesy, D. Cullen, R. T. Bronson, and W. G. Kaelin Jr
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Blood, March 15, 2008; 111(6): 3236 - 3244.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
V. H. Haase
Hypoxia-inducible factors in the kidney
Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
M. P. Biju, Y. Akai, N. Shrimanker, and V. H. Haase
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent
Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1217 - F1226.
[Abstract] [Full Text] [PDF]