Daily exposure to chlordecone, an organochlorine pesticide, increases cardiac fibrosis and atrial fibrillation vulnerability
Bibliographic record
Abstract
Chlordecone (CLD) is a carcinogenic organochlorine pesticide. CLD was shown to disturb the activity of cardiac Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase. Conditions affecting these transmembrane pumps are often associated with cardiac arrhythmias (CA). However, little is known about the role of CLD on atrial fibrillation (AF) incidence, the most common type of CA. 1) Daily ingestion of CLD induces arrhythmogenic cardiac remodeling. 2) A phase of CLD withdrawal can reduce CLD-induced AF susceptibility. Adult male Wistar rats (250 g-275 g) ingested daily-doses of CLD (0 μg/L, 0.1 μg/L, or 1 μg/L) diluted in their quotidian water for 4 weeks. From day (D)29 to D56, all rats received CLD-free water. Vulnerability to AF and cardiac function were evaluated at D28 and D56 by electrophysiological study, echocardiography, and optical-mapping. Levels of genes and proteins related to inflammation, fibrosis, and senescence were quantified by qPCR and immunoassays. Twenty-eight days of CLD exposure were associated with significantly increased AF vulnerability compared to CLD-free rats. Contamination with 1 μg/L CLD significantly reduced atrial conduction velocity (ERP, APD). CLD-weaning normalized food consumption and weight intake. However, after the CLD-withdrawal period of 28 days, AF inducibility, atrial inflammation (IL6, IL1β), and atrial fibrosis (Masson’s trichrome staining) remained significantly higher in rats exposed to 1 μg/L CLD compared to 0 μg/L. Prolonged CLD ingestion provokes atrial conduction slowing and increased risk of AF. Although CLD-weaning, some persistent damages occurred in the atrium like atrial fibrosis and atrial senescence signals, which are accompanied by atrial inflammation and arrhythmogenicity. Arrhythmogenic remodeling from prolonged CLD-poisoning to AF. Daily ingestion of concentrations of CLD above 0.1 µg/L is associated with increased atrial inflammation characterized by enhanced expression of pyroptosis promotor GSDMD (via pore-forming activity) and proinflammatory biomarkers such as NLRP3, IL1b, and IL6. Senescence markers p16 and p21 are also overexpressed in the heart. Atrial inflammation and senescence are accompanied by increased production of fibrous content and fibrosis biomarkers such as ACTA2, COL3A1, and TGFβ1. CLD-induced damaged atrial tissue also shows a reduction of key ion channels such as KCNQ1 and SCN5A involved in the cardiomyocytes’ action potential. Convergence of CLD-induced atrial toxicity via inflammation, senescence, fibrosis, and deregulated circulation of ions provoke reduction of conduction velocity, decreased ERP, and reduced APD. Altogether, these phenomena contribute to increasing the risk of atrial arrhythmias and AF. Abbreviations ACTA2 : alpha 2 smooth muscle actin , AF : atrial fibrillation, APD : action potential duration, CLD : chlordecone, COL : collagen, ERP : effective refractory period, GSDMD : gasdermin-D, IL : interleukin, KCNQ1 : potassium voltage-gated channel subfamily Q member 1, NLRP3 : NACHT, LRR, and PYD domain-containing protein 3, p16 : cyclin-dependent kinase inhibitor 2 A, p21 : cyclin-dependent kinase inhibitor 1, SCN5A : sodium voltage-gated channel alpha subunit 5, TGFβ1 : transforming growth factor beta 1. • CLD poisoning provokes atrial inflammation (IL1β and IL6). • CLD-induced atrial inflammation is accompanied by atrial fibrosis. • CLD-associated atrial fibrosis leads to conduction slowing and AF susceptibility. • CLD weaning might not be sufficient to reverse CLD-induced arrhythmogenic damages. • AF management might involve CLD-weaning combined with anti-inflammation strategies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".