Investigating the role of phosphorylated regulatory light chains during heart failure progression
It is established that enhanced Regulatory Light Chain (RLC) phosphorylation in muscle improves its contractility. Incidentally, it is observed that the levels are enhanced during the compensatory phase of heart failure (HF) and reduced in the decompensatory phase, where muscle contractility is c...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
| Published: |
Nanyang Technological University
2022
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/155766 https://doi.org/10.3390/ijms23010088 https://doi.org/10.3390/ijms22094351 https://doi.org/10.1002/cpz1.221 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | It is established that enhanced Regulatory Light Chain (RLC) phosphorylation in muscle
improves its contractility. Incidentally, it is observed that the levels are enhanced during the
compensatory phase of heart failure (HF) and reduced in the decompensatory phase, where
muscle contractility is compromised. However, it is not known if the changes in RLC
phosphorylation status drives the cardiac functional changes during HF progression or if HF
progression drives the changes in RLC phosphorylation status. Thus, the 28-day longitudinal
profiles of maximal isometric force and RLC phosphorylation were superimposed, and the
results suggest that RLC phosphorylation changes transiently to sustain contractility in the
compensatory phase. The potential of RLC in reversing contractile disease is explored by
enhancing RLC phosphorylation levels, via in vitro exchange methods, in muscle fibre in the
decompensatory phase. The enhancement improved contractility substantiating the use of
phosphorylated RLCs as small molecule treatment for HF. |
|---|