Detection and Proinflammatory Effects of BTEX within the Human Atherosclerotic Plaque
Bibliographic record
Abstract
-xylene isomers), and ethylbenzene (BTEX) are associated with an increased incidence of cardiovascular diseases. However, the underlying mechanisms are unknown. Here, we tested the hypothesis that BTEX accumulate in human atherosclerotic plaque, promoting local proinflammatory responses within atheroma tissues. To this aim, we retrospectively analyzed carotid plaque samples from 147 individuals from a cohort of people with asymptomatic carotid stenosis undergoing carotid endarterectomy. In atheroma specimens, we quantified BTEX and 1,4-benzoquinone, a benzene metabolite, through flame ionization detector gas chromatography and by high-performance liquid chromatography, respectively. We categorized individuals as BTEX-positive or BTEX-negative and compared the expression of plaque inflammatory markers in these two groups. To explore the mechanistic basis for our clinical observations, we also treated human monocytes with relevant concentrations of the four BTEX and evaluated their possible proinflammatory effect. Among the 147 plaques analyzed, 93 had evidence of at least one BTEX pollutant. Benzene was the most abundant, and its levels were positively correlated to those of 1,4-benzoquinone. Patients with evidence of BTEX within the atheroma, compared with those without, showed higher levels of CD68, MMP9, NLRP3, IL-1β, and TNF-α within the plaque but also of systemic markers of inflammation such as the white blood cell count and neutrophil-to-lymphocyte ratio. BTEX levels were positively correlated with NLRP3 and IL-1β levels as well as with triglyceride. BTEX levels were higher in people with a prior diagnosis of dyslipidemia and with a subsequent major cardiovascular event. Treatment of monocytes for 5 days with benzene, xylene, and ethylbenzene, but not toluene, fostered a consistent proinflammatory response, an effect observed in the absence of cytotoxicity and phenocopied by the treatment with 1,4-benzoquinone. BTEX and 1,4-benzoquinone also promoted foam cell formation in monocytes differentiated into macrophages. These data represent the first evidence that BTEX pollutants accumulate within the carotid plaque tissue. This phenomenon is associated with increased local inflammation, possibly suggesting the activation of proatherogenic pathways at the local level.
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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 | 0.001 | 0.001 |
| 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".