Skip Navigation


Cardiovascular Research Advance Access originally published online on July 16, 2008
Cardiovascular Research 2008 80(2):209-218; doi:10.1093/cvr/cvn198
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
80/2/209    most recent
cvn198v2
cvn198v1
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 Palpant, N. J.
Right arrow Articles by Metzger, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Palpant, N. J.
Right arrow Articles by Metzger, J. M.
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 2008. For permissions please email: journals.permissions@oxfordjournals.org

Single histidine-substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction

Nathan J. Palpant1, Sharlene M. Day1,2, Todd J. Herron1, Kimber L. Converso3 and Joseph M. Metzger1,2,*

1 Department of Molecular and Integrative Physiology, University of Michigan Medical School, 1301 E. Catherine Street, 7727 Medical Science II, Ann Arbor, MI 48109-0622, USA
2 Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3 Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA

* Corresponding author. Tel: +1 734 763 0560; fax: +1 734 647 6461. E-mail address: metzgerj{at}umich.edu

Aims: Contractile dysfunction associated with myocardial ischaemia is a significant cause of morbidity and mortality in the elderly. Strategies to protect the aged heart from ischaemia-mediated pump failure are needed. We hypothesized that troponin I-mediated augmentation of myofilament calcium sensitivity would protect cardiac function in aged mice.

Methods and results: To address this, we investigated transgenic (Tg) mice expressing a histidine-substituted form of adult cardiac troponin I (cTnI A164H), which increases myofilament calcium sensitivity in a pH-dependent manner. Serial echocardiography revealed that Tg hearts showed significantly improved systolic function at 4 months, which was sustained for 2 years based on ejection fraction and velocity of circumferential fibre shortening. Age-related diastolic dysfunction was also attenuated in Tg mice as assessed by Doppler measurements of the mitral valve inflow and lateral annulus Doppler tissue imaging. During acute hypoxia, cardiac contractility significantly improved in aged Tg mice made evident by increased stroke volume, end systolic pressure, and +dP/dt compared with non-transgenic mice.

Conclusion: This study shows that increasing myofilament function by means of a pH-responsive histidine button engineered into cTnI results in enhanced baseline heart function in Tg mice over their lifetime, and during acute hypoxia improves survival in aged mice by maintaining cardiac contractility.

KEYWORDS Troponin I; Ageing; Cardiac function; Hypoxia

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.