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Abstract 15338: The Essential Role of Fatty-Acid Binding Protein 3 in Endothelial Function

2022· article· en· W4380763343 on OpenAlexaff
Hien C. Nguyen, Shuhan Bu, David Michels, Sepideh Nikfarjam, Berk Rasheed, Mohammad Qadura, Krishna K. Singh

Bibliographic record

VenueCirculation · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPeroxisome Proliferator-Activated Receptors
Canadian institutionsUniversity of TorontoWestern University
Fundersnot available
KeywordsFatty acid-binding proteinUmbilical veinAngiogenesisMedicineGene silencingEndothelial stem cellInflammationEndotheliumDownregulation and upregulationLipopolysaccharideCell biologyImmunologyPharmacologyCancer researchBiologyInternal medicineIn vitroBiochemistryGene

Abstract

fetched live from OpenAlex

Background: The endothelium lines blood vessel’s inner walls and interacts directly with the circulation, systemically influencing whole-body physiology through endothelial function. Fatty acid binding protein 3 (FABP3), abundant in myocardiocytes, serve as effective cardiac injury’s biomarkers when presented in circulation. Our lab has preliminary found that endothelial cells (ECs) express FABP3. The role of FABP3 in endothelial function and FABP3 exposure’s effects on ECs are unknown. Objective: Evaluate FABP3’s role in endothelial dysfunction. Method: Human umbilical vein endothelial cells (HUVECs) were grown under cell culture standards (370 C, 5% CO2) prior to treatment by lipopolysaccharide (LPS). FABP3 expression in treated HUVECs was evaluated by qPCR. Next, FABP3-silencing RNAs were transfected into HUVECs to knock-down FABP3 for 24 hours. HUVECs were also exposed to recombinant FABP3 as a gain of function model. HUVECs were then treated with LPS for 24 hours before subjected to molecular/phenotypic evaluation for aspects of endothelial function (migration, proliferation, angiogenesis, inflammation). The Delta-Ct method and One-way ANOVA with Tukey (HSD) test were used to analyze data from qPCR and comparisons between treatment groups, respectively; p-value < 0.05 is considered significant. Results: 1) FABP3 is basally expressed in ECs, 2) LPS upregulated endothelial FABP3 expression; 3) loss of FABP3 protected ECs against LPS-induced endothelial dysfunction; FABP3 exposure exacerbated LPS-induced inflammation; 4) loss of FABP3 protects ECs against LPS-induced stress by promoting cell survival, anti-inflammatory and pro-angiogenic pathways. Conclusions: We identified the novel and basal expression of FABP3 in ECs and demonstrated that FABP3 influences endothelial function at both the molecular and phenotypic levels under stress in vitro. Loss- and gain- of endothelial FABP3 ameliorates and exacerbates LPS-induced endothelial dysfunction, respectively, by affecting cell survival and inflammatory and angiogenic pathways. Our findings suggest that circulating FABP3 may be detrimental to the endothelium; therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in myocardial injury.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.037

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0110.004

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.

Opus teacher head0.008
GPT teacher head0.219
Teacher spread0.212 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

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Citations1
Published2022
Admission routes1
Has abstractyes

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