Evidence map›Paper›PMID 32268788›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.

Longfei Wang, Gunner Halliday, Joshua R Huot, Taijyu Satoh, Jeffrey J Baust, Amanda Fisher, Todd Cook, Jian Hu, Theodore Avolio, Dmitry A Goncharov and 13 more

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. 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
3.1field-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

25 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Advances in extracardiac mechanisms for heart failure with preserved ejection fraction.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022
    Article
  18. Article
  19. Animal models of pulmonary hypertension due to left heart disease.Animal models and experimental medicine · 2022
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 4 institutions in 3 countries.

Longfei WangFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Gunner HallidayDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
Joshua R HuotDepartment of Surgery (J.R.H., A.B.), Indiana University School of Medicine, Indianapolis.
Taijyu SatohFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Jeffrey J BaustFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Amanda FisherDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
Todd CookDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
Jian HuFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Theodore AvolioFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Dmitry A GoncharovFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Yang BaiDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
Rebecca R VanderpoolDivision of Translational and Regenerative Medicine, University of Arizona, Tucson (R.R.V.).
Robert V ConsidineDivision of Endocrinology (R.V.C.), Indiana University School of Medicine, Indianapolis.
Andrea BonettoDepartment of Surgery (J.R.H., A.B.), Indiana University School of Medicine, Indianapolis.
Jiangning TanDivision of Pulmonary, Allergy and Critical Care Medicine (J.T., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Timothy N BachmanFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Andrea SebastianiFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Charles F McTiernanFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Ana L MoraFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Roberto F MachadoDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
Elena A GoncharovaFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Mark T GladwinFrom the Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute (L.W., T.S., J.J.B., J.H., T.A., D.A.G., T.N.B., A.S., C.F.M., A.L.M., E.A.G., M.T.G.), University of Pittsburgh, PA.
Yen-Chun LaiDivision of Pulmonary, Critical Care, Sleep and Occupational Medicine (G.H., A.F., T.C., Y.B., R.F.M., Y.-C.L.), Indiana University School of Medicine, Indianapolis.
University of Pittsburgh · USIndiana University School of MedicineIndiana University – Purdue University Indianapolis · USTohoku University · JP

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2011 to 2020
$26.1M
Translation CoreP30DK097512 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Carmella Evans-Molina · 2015 to 2026
$17.4M
Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisR01HL098032 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin · 2009 to 2026
$12.5M
Vascular Targeting Genomic & Genetic Strategies for Acute Chest SyndromeR01HL111656 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Roberto F. Machado · 2013 to 2026
$7.9M
Antidote for inhaled CO poisoning based on mutationally engineered neuroglobinR01HL125886 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin, Jesus Tejero Bravo · 2015 to 2026
$7.9M
Translational Pulmonary Vascular BiologyT32HL110849 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sruti Shiva · 2012 to 2026
$5.0M
Novel mechanisms of obliterative pulmonary vascular remodeling and sever pulmonary arterial hypertensionR01HL133951 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI ZHAO, YOU-YANG · 2016 to 2024
$4.9M
Role of Skeletal Muscle in Pulmonary Vascular RemodelingR01HL142638 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI Yen Chun Charly Lai · 2018 to 2026
$4.9M
Role of Sphingolipid Pathways in the Pathobiology of PAHR01HL127342 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MACHADO, ROBERTO F., NATARAJAN, VISWANATHAN · 2016 to 2023
$4.5M
Comprehensive Training Program in Musculoskeletal ResearchT32AR065971 · NIAMS · INDIANA UNIVERSITY INDIANAPOLIS · PI ALEXANDER G ROBLING · 2015 to 2026
$4.4M
HIPPO Signaling in Pulmonary Arterial HypertensionR01HL130261 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GONCHAROVA, ELENA · 2016 to 2023
$3.5M
TSC2 Signaling in Pulmonary Arterial HypertensionR01HL113178 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GONCHAROVA, ELENA · 2012 to 2021
$3.1M
NHLBI NIH HHS P01 HL103455NHLBI NIH HHS R01 HL098032NHLBI NIH HHS R01 HL111656NHLBI NIH HHS R01 HL113178NHLBI NIH HHS R01 HL125886NHLBI NIH HHS R01 HL127342NHLBI NIH HHS R01 HL130261NHLBI NIH HHS R01 HL142638NHLBI NIH HHS R01 HL150638NHLBI NIH HHS T32 HL110849NIAMS NIH HHS T32 AR065971NIDDK NIH HHS P30 DK097512
6 · The paper itself

Abstract

objectivePulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF. Approach and Results: Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.

conclusionsOur data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease.

Indexed as

AMP-Activated Protein KinasesAnimalsAntihypertensive AgentsDiet, High-FatEpoprostenolHeartHeart FailureHyperglycemiaHypertension, PulmonaryHypoglycemic AgentsInsulin ResistanceMaleMetabolic SyndromeMetforminMiceMice, Inbred C57BLAMP-Activated Protein KinasesAntihypertensive AgentsEpoprostenolHypoglycemic AgentsMetforminReceptors, Leptintreprostinilglucose intolerancemetabolic syndromemetformintreprostinil

Identifiers

PMID32268788
PMCPMC7255946
OpenAlexW3015741515

What Socratic holds

Texttitle and abstract
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 Socratic graph.