Investigating The Role Of Platelet Proteins In The Regulation Of Atherosclerosis In Coronary Artery Disease
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Investigating The Role Of Platelet Proteins In The
Regulation Of Atherosclerosis In Coronary
Artery Disease
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| Creator |
Das, Apabrita Ayan
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| Subject |
Cell Biology & Physiology
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| Description |
The role of inflammation in all stages of atherosclerotic process is well-known and soluble
TREM like transcript 1 (sTLT1), a platelet protein, is reported to be linked to chronic
inflammation. Yet, no information is available about the involvement of sTLT1 in
atherosclerotic cardiovascular disease. Initially, our results indicated plasma level of sTLT1
was significantly (p<0.05) elevated in clinical (2342±184pg/ml) and subclinical cases
(1773±118pg/ml) than healthy controls (461±57pg/ml). Additionally, statistical analyses
indicated that sTLT1 was associated with Coronary Artery Disease (CAD). Ex vivo studies
on macrophages indicated that sTLT1 binds to Fcɣ RI to activate MAP kinase signalling
cascade to activate NF-kB which promotes secretion of pro-inflammatory cytokine TNF-α
from macrophage cells. Atherosclerotic apoE-/- mice also showed high levels of sTLT1 and
TNF-α in virtually occluded aortic stage indicating the contribution of sTLT1 in
inflammation. As, sTLT1 is a platelet secreted protein with a significant role in CAD, we
explored the plasma secretome of Coronary Artery Disease subgroups (STEMI, NSTEMI,
UA) which may identify new candidate proteins responsible for the development of CAD.
It resulted into the identification of several unique proteins in each subgroup. Employing a
case-control design, more than 2500 annotated proteins were identified using Orbitrap mass
spectrometer in both STEMI and healthy control subjects; whereas in NSTEMI and UA the
numbers were a little less (>800). Quantitative proteomics study on STEMI patients revealed
that 26 proteins were decreased and 38 proteins were increased significantly in STEMI
compared to healthy control. AZGP1, ABCA5, Calicin, PGLYRP2, HAVCR2, C17ORF57
appeared to be relevant to STEMI whereas soluble Galectin-3 seemed relevant to NSTEMI
after cross-validation in human samples. Mechanistic significance in foam cells indicated the
imbalance of RCT through the interaction of AZGP1 with CD36. Additionally, in silico
studies of soluble Galectin-3 with Dectin-1 showed the activation of Dectin-1 mediated
signalling which led to the secretion of pro-inflammatory cytokines. In summary, this study
revealed a unique relationship of some novel proteins apparently responsible for impaired
RCT and chronic inflammation leading to atherothrombosis and myocardial infarction in
CAD.
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| Date |
2020
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2836/1/APABRITA_AYAN_DAS__THESIS.pdf
Das, Apabrita Ayan (2020) Investigating The Role Of Platelet Proteins In The Regulation Of Atherosclerosis In Coronary Artery Disease. PhD thesis, University of Calcutta. |
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| Relation |
http://www.eprints.iicb.res.in/2836/
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