Evidence map›Paper›PMID 21035466›Full record

ArticleLife sciences2011

Inducible COX-2 dominates over COX-1 in prostacyclin biosynthesis: mechanisms of COX-2 inhibitor risk to heart disease.

Cheng-Huai Ruan, Shui-Ping So, Ke-He Ruan

Abstract read
In one paragraph

Article in Life sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 73 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. The potential role of sesquiterpene lactones isolated from medicinal plants in the treatment of the metabolic syndrome - A review.South African journal of botany : official journal of the South African Association of Botanists = Suid-Afrikaanse tydskrif vir plantkunde : amptelike tydskrif van die Suid-Afrikaanse Genootskap van Plantkundiges · 2020
    Review
  15. Microvascular thrombosis: experimental and clinical implications.Translational research : the journal of laboratory and clinical medicine · 2020
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

3 authors at 2 institutions in 1 country.

Cheng-Huai RuanDepartment of Internal Medicine, New York Hospital Medical Center of Queens/Weil Cornell Medical College Affiliated Hospital, Flushing, NY 11355, United States. chr9062@nyp.org
Shui-Ping So
Ke-He Ruan
University of Houston · USCornell University · US

Funding

Prostaglandin I synthase, Thromboxane A synthase & Prostaglandin E synthaseR01HL056712 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI RUAN, KE-HE · 2000 to 2009
$2.3M
SHORT TERM RESEARCH TRAININGT35DK007676 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KONE, BRUCE C. · 1992 to 2017
$1.8M
STRUCTURE &FUNCTION RELATIONSHIP: PROSTANOID RECEPTORSR01HL079389 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI RUAN, KE-HE · 2005 to 2008
$1.4M
Prostacyclin-secreting Cells as Therapy for Pulmonary Artery HypertensionRC1HL100807 · NHLBI · TEXAS HEART INSTITUTE · PI DIXON, RICHARD A.F., RUAN, KE-HE · 2009 to 2010
$1.0M
PGI &TXA SYNTHASES--MEMBRANE ANCHOR STRUCTURE/FUNCTIONR29HL056712 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI RUAN, KE-HE · 1996 to 1999
–
NHLBI NIH HHS HL100807NHLBI NIH HHS HL56712NHLBI NIH HHS HL79389NHLBI NIH HHS R01 HL056712NHLBI NIH HHS R01 HL079389NHLBI NIH HHS R29 HL056712NHLBI NIH HHS RC1 HL100807NIDDK NIH HHS T35 DK007676NIDDK NIH HHS T5 DK007676
6 · The paper itself

Abstract

aimOur aim is to understand the molecular mechanisms of the selective nonsteroidal anti-inflammatory drugs (NSAID), cyclooxygenase-2 (COX-2) inhibitors', higher "priority" to reduce synthesis of the vascular protector, prostacyclin (PGI2), compared to that of nonselective NSAIDs. MAIN

methodsCOX-1 or COX-2 was co-expressed with PGI2 synthase (PGIS) in COS-7 cells. The Km and initial velocity (½t Vmax) of the coupling reaction between COX-1 and COX-2 to PGIS were established. The experiment was further confirmed by a kinetics study using hybrid enzymes linking COX-1 or COX-2 to PGIS. Finally, COX-1 or COX-2 and PGIS were respectively fused to red (RFP) and cyanic (CFP) fluorescence proteins, and co-expressed in cells. The distances between COXs and PGIS were compared by FRET. KEY

findingsThe Km for converting arachidonic acid (AA) to PGI2 by COX-2 coupled to PGIS is ~2.0μM; however, it was 3-fold more (~6.0μM) for COX-1 coupled to PGIS. The Km and ½t Vmax for COX-2 linked to PGIS were ~2.0μM and 20s, respectively, which were 2-5 folds faster than that of COX-1 linked to PGIS. The FRET study found that the distance between COX-2-RFP and PGIS-CFP is shorter than that between COX-1-RFP and PGIS-CFP. SIGNIFICANCE: The study provided strong evidence suggesting that the low Km, faster ½t Vmax, and closer distance are the basis for COX-2 dominance over COX-1 (coupled to PGIS) in PGI2 synthesis, and further demonstrated the mechanisms of selective COX-2 inhibitors with higher potential to reduce synthesis of the vascular protector, PGI2.

Indexed as

AnimalsArachidonic AcidBlotting, WesternCardiovascular DiseasesChlorocebus aethiopsChromatography, High Pressure LiquidCOS CellsCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase 2 InhibitorsElectrophoresis, Polyacrylamide GelEpoprostenolMicroscopy, FluorescenceArachidonic AcidCyclooxygenase 1Cyclooxygenase 2Cyclooxygenase 2 InhibitorsEpoprostenol

Identifiers

PMID21035466
PMCPMC3046773
OpenAlexW2077923150

What OpenQuestion holds

Textmetadata
LicenceTDM
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.