Abstract 11922: Adiponectin Limits Monocytic Microparticle-Induced Inflammasome Activation and Endothelial Dysfunction
Bibliographic record
Abstract
Introduction: Monocytic microparticles (mono-MPs) play a fundamental role in the atherothrombotic process. Alterations in monocyte-endothelial cell (EC) interaction mediate immune activation and propagate inflammation. Adiponectin primes monocyte differentiation into anti-inflammatory M2 vs. pro-inflammatory M1 macrophages and inhibits EC activation. Hypothesis: We hypothesized that mono-MPs trigger NLRP3 inflammasome-dependent EC activation and adiponectin inhibits this phenomenon, in part, through limiting mono-MP production and activation. Methods: Mono-MPs were characterized using electron microscopy, flow cytometry and NanoSight microscopy. Exosomes were excluded based on size and absence of the exosome-specific markers. Studies were conducted with THP-1 monocytes and peritoneal monocytes from adiponectin knockout (Adipoq-/-) mice. We evaluated the effects of lipopolysaccharide (LPS; 5 μg/ml, 24 h) and recombinant adiponectin (10 μg/ml) on mono-MP production, expression of the NLRP3 inflammasome and its components, and key downstream inflammatory factors. We also studied how MPs alter the expression of critical adhesion molecules and inflammatory transcription factors in HUVEC cultures. Inflammasome activation was examined in mono-MPs derived from THP-1 cells. Results: Adiponectin suppressed LPS-induced MP generation by THP-1 monocytes. LPS-treated mono-MPs exhibited a marked upregulation in NLRP3 inflammasomes and NLRP3 components (ASC, caspase-1, pro-IL1β and IL1β). Adiponectin attenuated these changes. Adiponectin inhibited the significant increases in ICAM-1, VCAM-1, p-IkB, p-NFkB and p-ERK-1 noted in mono-MP-HUVEC co-cultures. Compared to monocytes from Adipoq+/+ mice, those from Adipoq-/- littermates showed a ~6-fold greater production of MPs following LPS stimulation. Conclusions: We report a novel mechanism through which mono-MPs sustain NLRP3 inflammasome activation and endothelial dysfunction. These data reveal a previously unknown atheroprotective mechanism for adiponectin that may account for the inverse relationship between circulating adiponectin levels and the risk of diabetes and obesity.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".