Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on March 10, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp085
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
83/2/294    most recent
cvp085v2
cvp085v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Luan, R.
Right arrow Articles by Tao, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luan, R.
Right arrow Articles by Tao, L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

High glucose Sensitizes Adult Cardiomyocytes to Ischemia/Reperfusion Injury Through Nitrative Thioredoxin Inactivation

Ronghua Luan, MD1, Shaowei Liu, MD1, Tao Yin, MD1, Wayne Bond Lau, MD2, Qun Wang, MD, PhD1, Wenyi Guo, MD, PhD1, Haichang Wang, MD, PhD1,* and Ling Tao, MD, PhD1,*

1 Department of Cardiology, Xijing Hospital, The Fourth Military Medical University Xian, China, 710032
2 Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107

* Address proofs to: Ling Tao, M.D., Ph.D., Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, 15 West Changle Road, Xian, China, 710032, Tel: (8629)847-75183, Fax: (8629) 847-71170, E-mail: Lingtao2006{at}gmail.com Or Haichang Wang, MD, PhD, Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, 15 West Changle Road, Xian, China, 710032, Tel: (8629)847-73469, Fax: (8629) 847-71170 E-mail: wanghc{at}fmmu.edu.cn

Aims: Ischemic cardiac injury is significantly increased in diabetic patients, but its underlying mechanisms remain incompletely understood. The current study attempted to identify new molecular mechanisms potentially contributive to hyperglycemic-exaggeration of myocardial ischemic injury.

Methods: Adult mouse cardiomyocytes were cultured in normal-glucose (NG, 5.5 mM) or high-glucose (HG, 25 mM) medium. 12 hours after NG or HG pre-culture, cardiomyocytes were subjected to 3 hours of simulated ischemia (SI), followed by 3 hours of reperfusion (R) in NG medium. Prior to and after SI/R, the following were determined: cardiomyocyte death and apoptosis, sustained oxidative/nitrative stress, and thioredoxin (Trx) activity, expression, and nitration.

Results: Compared to NG-cultured cardiomyocytes, 12-hour HG culture significantly increased superoxide and peroxynitrite production, increased Trx-1 nitration, and reduced Trx activity (P<0.01). Despite being subject to identical SI/R procedures and conditions, cells pre-cultured in HG sustained greater injury, evidenced by elevated lactate dehydrogenase (LDH) release and caspase-3 activation (P<0.01). Moreover, SI/R induced greater superoxide/peroxynitrite overproduction and greater Trx-1 nitration and inactivation in HG pre-cultured cardiomyocytes than in NG pre-cultured cardiomyocytes. Finally, the supplementation of human Trx-1, superoxide scavenger, or peroxynitrite decomposition catalyst in HG pre-cultured cells reduced Trx-1 nitration, preserved Trx-1 activity, and normalized SI/R injury to levels observed in NG pre-cultured cardiomyocytes.

Conclusions: High glucose sensitized cardiomyocytes to ischemia/reperfusion injury through nitrative Trx-1 inactivation. Interventions restoring Trx-1 activity in the diabetic heart may represent novel therapies attenuating cardiac injury in diabetic patients.

KEYWORDS Diabetes; Thioredoxin; Protein Nitration; Ischemia/Reperfusion

Time for primary review: 19 Days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.