Evidence map›Paper›PMID 31154939›Full record

ArticleCirculation research2019

Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease.

Benoît Ranchoux, Valérie Nadeau, Alice Bourgeois, Steeve Provencher, Éve Tremblay, Junichi Omura, Nancy Coté, Rami Abu-Alhayja'a, Valérie Dumais, Renato T Nachbar and 11 more

Abstract read
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In one paragraph

Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 105 citations in OpenAlex.

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  10. Non-Surgical Periodontal Therapy and Metformin Improve Bone Loss in Obese Mice With Periodontitis by Modulating the Gut Microbiota.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  11. Review
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  13. Dysregulated fatty acid metabolism in pericardiac adipose tissue of pulmonary hypertension due to left heart disease mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 1 country.

Benoît RanchouxFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Valérie NadeauFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Alice BourgeoisFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Steeve ProvencherFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Éve TremblayFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Junichi OmuraFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Nancy CotéFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Rami Abu-Alhayja'aFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Valérie DumaisInstitut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, Canada (V.D., R.T.N., A.M.).
Renato T NachbarInstitut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, Canada (V.D., R.T.N., A.M.).
Lionel TastetFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Abdellaziz DahouFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Sandra Breuils-BonnetFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
André MaretteInstitut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Québec City, Canada (V.D., R.T.N., A.M.).
Philippe PibarotFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Jocelyn DupuisInstitut de cardiologie de Montréal, Québec, Canada (J.D.).
Roxane PaulinFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Olivier BoucheratFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Stephen L ArcherDepartment of Medicine, Queen's University, Kingston, Ontario, Canada (S.L.A., F.P.).
Sébastien BonnetFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
François PotusFrom the Pulmonary Hypertension Research Group of the Institut Universitaire de Cardiologie et de Pneumologie de Québec Research Center, Laval University, Québec City, Canada (B.R., V.N., A.B., S.P., E.T., J.O., N.C., R.A-A., L.T., A.D., S.B.-B., P.P., R.P., O.B., S.B., F.P.).
Institut Universitaire de Cardiologie et de Pneumologie de Québec · CAUniversité Laval · CA

Funding

CIHR
6 · The paper itself

Abstract

rationalePulmonary hypertension (PH) due to left heart disease (LHD), or group 2 PH, is the most prevalent form of PH worldwide. PH due to LHD is often associated with metabolic syndrome (MetS). In 12% to 13% of cases, patients with PH due to LHD display vascular remodeling of pulmonary arteries (PAs) associated with poor prognosis. Unfortunately, the underlying mechanisms remain unknown; PH-targeted therapies for this group are nonexistent, and the development of a new preclinical model is crucial. Among the numerous pathways dysregulated in MetS, inflammation plays also a critical role in both PH and vascular remodeling.

objectiveWe hypothesized that MetS and inflammation may trigger the development of vascular remodeling in group 2 PH. METHODS AND

resultsUsing supracoronary aortic banding, we induced diastolic dysfunction in rats. Then we induced MetS by a combination of high-fat diet and olanzapine treatment. We used metformin treatment and anti-IL-6 (interleukin-6) antibodies to inhibit the IL-6 pathway. Compared with sham conditions, only supracoronary aortic banding+MetS rats developed precapillary PH, as measured by both echocardiography and right/left heart catheterization. PH in supracoronary aortic banding+MetS was associated with macrophage accumulation and increased IL-6 production in lung. PH was also associated with STAT3 (signal transducer and activator of transcription 3) activation and increased proliferation of PA smooth muscle cells, which contributes to remodeling of distal PA. We reported macrophage accumulation, increased IL-6 levels, and STAT3 activation in the lung of group 2 PH patients. In vitro, IL-6 activates STAT3 and induces human PA smooth muscle cell proliferation. Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation. In vivo, in the supracoronary aortic banding+MetS animals, reducing IL-6, either by anti-IL-6 antibody or metformin treatment, reversed pulmonary vascular remodeling and improve PH due to LHD.

conclusionsWe developed a new preclinical model of group 2 PH by combining MetS with LHD. We showed that MetS exacerbates group 2 PH. We provided evidence for the importance of the IL-6-STAT3 pathway in our experimental model of group 2 PH and human patients.

Indexed as

Disease Models, AnimalAnimalsCells, CulturedDiet, High-FatHumansHypertension, PulmonaryInterleukin-6MacrophagesMaleMetabolic SyndromeOlanzapinePulmonary ArteryRatsRats, WistarVascular RemodelingVentricular DysfunctionInterleukin-6Olanzapinehypertension, pulmonaryinflammationinterleukin-6leptinmetabolic syndromemetforminventricular dysfunction, left

Identifiers

PMID31154939
OpenAlexW2949017320

What OpenQuestion holds

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Registered trials

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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.