Evidence map›Paper›PMID 32478115›Full record

ReviewGlobal cardiology science & practice2020

Inflammation, immunity, and vascular remodeling in pulmonary hypertension; Evidence for complement involvement?

Maria G Frid, Joshua M Thurman, Kirk C Hansen, Bradley A Maron, Kurt R Stenmark

Open access · diamondAbstract readReview
In one paragraph

Review in Global cardiology science & practice, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-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

29 citing papers in PubMed, 33 citations in OpenAlex.

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  13. Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024
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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

5 authors at 3 institutions in 1 country.

Maria G FridUniversity of Colorado, Denver, Anschutz Medical Campus, USA.
Joshua M ThurmanUniversity of Colorado, Denver, Anschutz Medical Campus, USA.
Kirk C HansenUniversity of Colorado, Denver, Anschutz Medical Campus, USA.
Bradley A MaronBrigham and Women's Hospital, Harvard Medical School, USA.
Kurt R StenmarkUniversity of Colorado, Denver, Anschutz Medical Campus, USA.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USHarvard University · US

Funding

VRAC and Rho in pulmonary EC proliferationP01HL014985 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI STENMARK, KURT R. · 1985 to 2019
$35.1M
Role of Complement-Driven Pulmonary Vascular Inflammation in PHP01HL152961 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI DELANEY, CASSIDY A · 2020 to 2024
$14.1M
The Complement System and Ischemic Acute Renal FailureR01DK076690 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Joshua M Thurman · 2008 to 2026
$6.6M
Immunologic Mechanisms of Progressive GlomerulosclerosisR01DK113586 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI THURMAN, JOSHUA M · 2017 to 2020
$1.4M
Quadrupole-Orbitrap Mass SpectrometerS10OD021641 · OD · UNIVERSITY OF COLORADO DENVER · PI HANSEN, KIRK C · 2017 to 2017
$600k
NHLBI NIH HHS P01 HL014985NHLBI NIH HHS P01 HL152961NIDDK NIH HHS R01 DK076690NIDDK NIH HHS R01 DK113586NIH HHS S10 OD021641
6 · The paper itself

Abstract

Pulmonary (arterial) hypertension (PH/PAH) is a life-threatening cardiopulmonary disorder. Experimental evidence suggests involvement of inflammatory and autoimmune processes in pathogenesis of PH/PAH, however the triggering and disease-promoting mechanisms remain unknown. The complement system is a key arm of innate immunity implicated in various pro-inflammatory and autoimmune diseases, yet, surprisingly little is known about the role of complement in PH/PAH pathogenesis. The preponderance of the existing data associates complement with PH/PAH via analysis of plasma and does not study the lung directly. Therefore, we aimed to resolve this by analyzing both the mechanisms of local lung-specific complement activation and the correlation of dysregulated plasma complement to clinical outcome in PAH patients. In our recent studies, reviewed herein, we show, for the first time, that  immunoglobulin-driven activation of the complement cascade, specifically its alternative pathway, in the pulmonary perivascular areas, is a key mechanism initiating pro-inflammatory processes in the early stage of experimental hypoxic PH (a form of "sterile inflammation"). In human patients with end-stage PAH, we have demonstrated that perivascular deposition of immunoglobulin G (IgG) and activation of the complement cascade are "longitudinally" persistent in the disease. We also showed, using unbiased network analysis, that plasma complement signaling, including again the Alternative pathway, is a prognostic factor of survival in patients with idiopathic PAH (IPAH). Based on these initial findings, we suggest that vascular-specific, immunoglobulin-driven dysregulated complement signaling triggers and maintains pulmonary vascular remodeling and PH. Future experiments in this area would facilitate discoveries on whether complement signaling can serve both as a biomarker and therapeutic target in PH/PAH.

Identifiers

PMID32478115
PMCPMC7232865
OpenAlexW3016489688

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.