From biomarker to therapeutic target : the role of myo-inositol and SMIT1 in heart failure and cardiac fibrosis
Bibliographic record
Abstract
Heart failure (HF) is a complex syndrome in which metabolic disturbances contribute significantly to disease progression. Among these, the cyclic polyol myo-inositol has recently emerged as a metabolite of interest. Transported into the heart by the sodium/myo-inositol transporter 1 (SMIT1), myo-inositol has been implicated in oxidative stress and maladaptive remodelling, yet its clinical and mechanistic relevance in heart failure has not been fully defined. In two large patient cohorts from Belgium and Canada, plasma myo-inositol concentrations were consistently higher in patients with HF than in controls, with the highest levels observed in HFpEF. In this subgroup it was independently associated with impaired renal function, poor clinical outcomes, and structural remodelling markers, particularly fibrotic. These observations suggest that circulating myo-inositol might not only be a biomarker but also a potential contributor to the pathogenesis of HFpEF. Mechanistic studies support this hypothesis. In vitro, exposure of human cardiac fibroblasts to myo-inositol stimulated proliferation, migration, and differentiation into contractile myofibroblasts, thereby enhancing extracellular matrix production. In HFrEF human hearts, SMIT1 expression was markedly increased in fibrotic regions, and transcriptomic analyses linked its upregulation to pro-fibrotic signaling networks. Consistently, mouse models of myocardial infarction demonstrated increased SMIT1 expression in areas of fibrosis. Moreover, cardiac fibroblasts derived from SMIT1-deficient mice showed blunted responses to TGF-β, with reduced myofibroblast differentiation, contractility, and collagen deposition. Taken together, these findings identify the myo-inositol/SMIT1 axis as a key driver of fibroblast activation and myocardial fibrosis. Elevated plasma myo-inositol provides prognostic information in HF, particularly HFpEF, while SMIT1-mediated transport enables the cellular processes that underlie adverse remodelling. This integrative evidence highlights the myo-inositol/SMIT1 pathway as both a marker of disease severity and a potential therapeutic target to mitigate fibrosis and improve outcomes in HF.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 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".