Evidence map›Paper›PMID 27456128›Full record

ArticleThe American journal of pathology2016

Increased Pyruvate Dehydrogenase Kinase 4 Expression in Lung Pericytes Is Associated with Reduced Endothelial-Pericyte Interactions and Small Vessel Loss in Pulmonary Arterial Hypertension.

Ke Yuan, Ning-Yi Shao, Jan K Hennigs, Marielle Discipulo, Mark E Orcholski, Elya Shamskhou, Alice Richter, Xinqian Hu, Joseph C Wu, Vinicio A de Jesus Perez

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The American journal of pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 54 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Deciphering the Complexities of Pulmonary Hypertension: The Emergent Role of Single-Cell Omics.American journal of respiratory cell and molecular biology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Mural Cell SDF1 Signaling Is Associated with the Pathogenesis of Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2020
    Article
  20. Metabolic Coordination of Pericyte Phenotypes: Therapeutic Implications.Frontiers in cell and developmental biology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Ke YuanDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California; Stanford Cardiovascular Institute, Stanford University, Stanford, California.
Ning-Yi ShaoStanford Cardiovascular Institute, Stanford University, Stanford, California; Division of Cardiology, Stanford University, Stanford, California.
Jan K HennigsStanford Cardiovascular Institute, Stanford University, Stanford, California; Department of Pediatrics, Stanford University, Stanford, California.
Marielle DiscipuloDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California.
Mark E OrcholskiDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California; Stanford Cardiovascular Institute, Stanford University, Stanford, California.
Elya ShamskhouDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California; Stanford Cardiovascular Institute, Stanford University, Stanford, California.
Alice RichterDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California.
Xinqian HuDepartment of Genetics, Stanford University, Stanford, California.
Joseph C WuStanford Cardiovascular Institute, Stanford University, Stanford, California; Division of Cardiology, Stanford University, Stanford, California.
Vinicio A de Jesus PerezDivision of Pulmonary and Critical Care Medicine, Stanford University, Stanford, California; Stanford Cardiovascular Institute, Stanford University, Stanford, California. Electronic address: vdejesus@stanford.edu.
Stanford University · USCardiovascular Institute of the South · US

Funding

The role of the Wnt/planar cell polarity pathway in pulmonary angiogenesisK08HL105884 · NHLBI · STANFORD UNIVERSITY · PI DE JESUS PEREZ, VINICIO A · 2012 to 2016
$701k
NHLBI NIH HHS K08 HL105884
6 · The paper itself

Abstract

Reduced endothelial-pericyte interactions are linked to progressive small vessel loss in pulmonary arterial hypertension (PAH), but the molecular mechanisms underlying this disease remain poorly understood. To identify relevant gene candidates associated with aberrant pericyte behavior, we performed a transcriptome analysis of patient-derived donor control and PAH lung pericytes followed by functional genomics analysis. Compared with donor control cells, PAH pericytes had significant enrichment of genes involved in various metabolic processes, the top hit being PDK4, a gene coding for an enzyme that suppresses mitochondrial activity in favor of glycolysis. Given reports that link reduced mitochondrial activity with increased PAH cell proliferation, we hypothesized that increased PDK4 is associated with PAH pericyte hyperproliferation and reduced endothelial-pericyte interactions. We found that PDK4 gene and protein expression was significantly elevated in PAH pericytes and correlated with reduced mitochondrial metabolism, higher rates of glycolysis, and hyperproliferation. Importantly, reducing PDK4 levels restored mitochondrial metabolism, reduced cell proliferation, and improved endothelial-pericyte interactions. To our knowledge, this is the first study that documents significant differences in gene expression between human donor control and PAH lung pericytes and the link between mitochondrial dysfunction and aberrant endothelial-pericyte interactions in PAH. Comprehensive characterization of these candidate genes could provide novel therapeutic targets to improve endothelial-pericyte interactions and prevent small vessel loss in PAH.

Indexed as

Blotting, WesternEndothelial CellsFlow CytometryFluorescent Antibody TechniqueGene Expression ProfilingGene Knockdown TechniquesHumansHypertension, PulmonaryOligonucleotide Array Sequence AnalysisPericytesPolymerase Chain ReactionProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseTranscriptomePDK4 protein, humanProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring Kinase

Identifiers

PMID27456128
PMCPMC5012507
OpenAlexW2496315847

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.