Abstract
Our earlier work has shown inter‑disease and intra‑disease differences in the cardiac proteome between right (RV) and left (LV) ventricles of patients with aortic valve stenosis (AVS) or coronary artery disease (CAD). Whether disease remodeling also affects acute changes occuring in the proteome during surgical intervention is unknown. This study investigated the effects of cardioplegic arrest on cardiac proteins/phosphoproteins in LV and RV of CAD (n=6) and AVS (n=6) patients undergoing cardiac surgery. LV and RV biopsies were collected during surgery before ischemic cold blood cardioplegic arrest (pre) and 20 min after reperfusion (post). Tissues were snap frozen, proteins extracted, and the extracts were used for proteomic and phosphoproteomic analysis using Tandem Mass Tag (TMT) analysis. The results were analysed using QuickGO and Ingenuity Pathway Analysis softwares. For each comparision, our proteomic analysis identified more than 3,000 proteins which could be detected in both the pre and Post samples. Cardioplegic arrest and reperfusion were associated with significant differential expression of 24 (LV) and 120 (RV) proteins in the CAD patients, which were linked to mitochondrial function, inflammation and cardiac contraction. By contrast, AVS patients showed differential expression of only 3 LV proteins and 2 RV proteins, despite a significantly longer duration of ischaemic cardioplegic arrest. The relative expression of 41 phosphoproteins was significantly altered in CAD patients, with 18 phosphoproteins showing altered expression in AVS patients. Inflammatory pathways were implicated in the changes in phosphoprotein expression in both groups. Inter‑disease comparison for the same ventricular chamber at both timepoints revealed differences relating to inflammation and adrenergic and calcium signalling. In conclusion, the present study found that ischemic arrest and reperfusion trigger different changes in the proteomes and phosphoproteomes of LV and RV of CAD and AVS patients undergoing surgery, with markedly more changes in CAD patients despite a significantly shorter ischaemic period.
| Original language | English |
|---|---|
| Article number | 77 |
| Number of pages | 14 |
| Journal | International Journal of Molecular Medicine |
| Volume | 49 |
| Issue number | 6 |
| Early online date | 14 Apr 2022 |
| DOIs | |
| Publication status | E-pub ahead of print - 14 Apr 2022 |
Bibliographical note
Funding Information:work are a sub‑study of a two‑centre randomized controlled trial investigating the effect of the upper limb remote isch‑ emic preconditioning (RIPc) in patients undergoing isolated coronary artery bypass grafting and/or aortic valve replace‑ ment on cardiac injury, metabolic stress and inflammatory response (12,13). The trial was conducted in accordance with the declaration of Helsinki at the Hammersmith Hospital and the Bristol Royal Infirmary. It was sponsored by the Imperial college of London, approved by the London‑Harrow Research Ethics committee (REc number 12/LO/1361) and registered to the International Standard Randomized controlled Trial Number (ISRcTN) registry (Id 33084113).
Funding Information:
This study was funded/supported by the British Heart Foundation (RG/15/5/31446) and the NIHR Biomedical Research centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol (UK).
Publisher Copyright:
© 2022 Spandidos Publications. All rights reserved.
Research Groups and Themes
- BTC (Bristol Trials Centre)
- Bristol Heart Institute
Keywords
- Proteomics
- human
- cardiac
- coronary artery disease
- aortic valve stenosis
- cardioplegic arrest
- ischemia
- ventricular biopsies
- TMT tag
- mass spectrometry