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Heparin-like molecules inhibit pulmonary vascular pericyte proliferation in vitro

2000· article· en· W2279411086 on OpenAlexaff
Joseph D. Khoury, David Langleben

Bibliographic record

VenueAmerican Journal of Physiology-Lung Cellular and Molecular Physiology · 2000
Typearticle
Languageen
FieldMedicine
TopicPulmonary Hypertension Research and Treatments
Canadian institutionsMcGill UniversityJewish General Hospital
Fundersnot available
KeywordsHeparinCell biologyVascular smooth muscleHeparan sulfateCell growthExtracellular matrixPericyteIn vitroChemistryBiologyPharmacologyEndothelial stem cellEndocrinologyBiochemistrySmooth muscle

Abstract

fetched live from OpenAlex

Proliferation of vascular pericytes (PCs), smooth muscle-like cells found in the distal microvasculature, contributes to vascular remodeling in pulmonary hypertension. The factors controlling lung PC quiescence in normal states are poorly understood. We demonstrate that exogenous heparin and heparan sulfate proteoglycans inhibit rat lung PC proliferation in vitro as does pulmonary vascular subendothelial matrix, particularly its heparan sulfate component. Heparin inhibits the intracellular alkalinization essential to proliferation, and we show that inhibition of alkalinization by 5-(N, N-dimethyl)amiloride also reduces PC proliferation. As shown by DNA staining and fluorescence-activated cell sorting analysis, heparin does not induce apoptosis in PCs. However, heparin maintains lung PCs in the G(0)/G(1) growth phase. Heparin induces production of p21, a potent inhibitor of cyclin-dependent kinases, thereby potentially identifying a fundamental mechanism by which heparin inhibits proliferation in smooth muscle-like cells. These studies establish additional similarities between lung PCs and smooth muscle cells and provide further understanding of growth control in the lung microvasculature. They also further support the rationale that heparin-like molecules might be therapeutically beneficial in pulmonary hypertension.

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 score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.006
GPT teacher head0.242
Teacher spread0.236 · 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".

Quick stats

Citations17
Published2000
Admission routes1
Has abstractyes

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Same venueAmerican Journal of Physiology-Lung Cellular and Molecular PhysiologySame topicPulmonary Hypertension Research and TreatmentsFrench-language works237,207