Imperial College London
Alternate

ProfessorStuartCook

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 1346stuart.cook

 
 
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Location

 

RF 16Sydney StreetRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ye:2018:10.1371/journal.pone.0201498,
author = {Ye, L and Su, L and Wang, C and Loo, S and Tee, G and Tan, S and Khin, SW and Ko, S and Su, B and Cook, SA},
doi = {10.1371/journal.pone.0201498},
journal = {PLoS One},
title = {Truncations of the titin Z-disc predispose to a heart failure with preserved ejection phenotype in the context of pressure overload},
url = {http://dx.doi.org/10.1371/journal.pone.0201498},
volume = {13},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Titin (TTN) Truncating variants (TTNtv) in the A-band of TTN predispose the mouse heart to systolic dysfunction when subjected to pressure-loading. However, the effects of TTNtv of the Z-disc are largely unexplored. A rat model of pressure-loaded heart is developed by trans-aortic constriction (TAC). Rats with TTNtv of the Z-disc were randomly assigned to TAC (Z-TAC) or sham-surgery (Z-Sham) and wildtype (WT) littermates served as controls (WT-TAC or WT-Sham). Left ventricular (LV) function was assessed by echocardiography. Pressure volume (PV) loops, histology and molecular profiling were performed eight months after surgery. Pressure-load by TAC increased LV mass in all cases when compared with Sham animals. Notably, systolic function was preserved in TAC animals throughout the study period, which was confirmed by terminal PV loops. Diastolic function was impaired in Z-disc TTNtv rats at baseline as compared to WT and became impaired further after TAC (dp/dtmin, mmHg/s): Z-TAC = -3435±763, WT-TAC = -6497±1299 (p<0.01). Z-TAC animals had greater cardiac fibrosis, with elevated collagen content and decreased vascular density as compared to WT-TAC animals associated with enhanced apoptosis of myocyte and non-myocyte populations. In the context of pressure overload, Z-disc TTNtv is associated with cardiac fibrosis, diastolic dysfunction, and capillary rarefaction in the absence of overt systolic dysfunction.
AU  - Ye,L
AU  - Su,L
AU  - Wang,C
AU  - Loo,S
AU  - Tee,G
AU  - Tan,S
AU  - Khin,SW
AU  - Ko,S
AU  - Su,B
AU  - Cook,SA
DO  - 10.1371/journal.pone.0201498
PY  - 2018///
TI  - Truncations of the titin Z-disc predispose to a heart failure with preserved ejection phenotype in the context of pressure overload
T2  - PLoS One
UR  - http://dx.doi.org/10.1371/journal.pone.0201498
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30063764
UR  - http://hdl.handle.net/10044/1/62774
VL  - 13
ER  -
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