OxPCs‐Mediated Lipid Metabolic Responses in Cardiomyocytes as well as During Ischemia Reperfusion Injury
Bibliographic record
Abstract
Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake through its receptor (LOX‐1) in a variety of physiological and pathological states. We investigated whether the proinflammatory effect of OxPL, generated during stress conditions such as ex‐vivo exposure to POVPC (1‐Palmitoyl‐2‐(5‐oxovaleroyl)‐sn‐glycero‐3‐phosphorylcholine), a derivative of oxidative phosphatidylcholines (OxPCs) of OxPL family and global heart ischemia/reperfusion (I/R), is through the activation of LOX‐1 as well as toll‐like receptor‐2 (TLR‐2). In this study, isolated cardiomyocytes exposed to POVPC as well as isolated rat hearts subjected to global I/R were analyzed. OxPCs‐mediated‐oxidative stress (OS), caused LOX‐1 activation and altered lipid homeostasis. There was an upregulation of TLR2 expression in these conditions, suggesting that TLR2‐mediated inflammation is through LOX1. Furthermore, phosphorylation of sterol regulatory element binding protein 1c (SREBP 1c) was also found be increased due to an increase in OxPCs levels, which is also promoted OS and cell death. On the other hand, LOX‐1 activation also upregulated SREBP1c‐mediated TGF‐βRII expression causing fibrosis. Out of 80 fragmented and non‐fragmented OxPCs followed in a heatmap analysis, 24 in cardiomyocytes and 25 in heart were significantly higher in these stress conditions. Eight (8) of the OxPCs were shared between cardiomyocytes and hearts (FDR < 0.001). Interestingly, one specific fragmented OxPC i.e. 1‐palmitoyl‐2‐azelaoyl‐sn‐glycero‐3‐phosphocholine (PAzPC) among 8 shared OxPCs, was common in both stress conditions. However, a second major fragmented OxPC i.e. 1‐stearoyl‐2‐azelaoyl‐sn‐glycerophosphocholine (SAzPC) was also upregulated in the heart but not in the cardiomyocyte. It appears that cardiomyocyte‐specific; PAzPC and heart‐specific; SAzPC OxPCs may mediate abnormal lipid metabolic responses causing inflammation, apoptosis and fibrosis. Support or Funding Information Canadian Institutes of Health Research and Research Manitoba This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".