Evidence map›Paper›PMID 23612967›Full record

ArticleThe Journal of biological chemistry2013

A molecular mechanism for therapeutic effects of cGMP-elevating agents in pulmonary arterial hypertension.

Raphaela Schwappacher, Ana Kilic, Baktybek Kojonazarov, Michaela Lang, Thuan Diep, Shunhui Zhuang, Thomas Gawlowski, Ralph T Schermuly, Alexander Pfeifer, Gerry R Boss and 1 more

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

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

16 citing papers in PubMed, 24 citations in OpenAlex.

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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

11 authors at 3 institutions in 2 countries.

Raphaela SchwappacherDepartment of Medicine, University of California San Diego, La Jolla, California 92093. Electronic address: rschwappacher@ucsd.edu.
Ana KilicInstitute for Pharmacology and Toxicology, University of Bonn, 53113 Bonn, Germany.
Baktybek KojonazarovUniversity of Giessen and Marburg Lung Center, 35392 Giessen, Germany.
Michaela LangUniversity of Giessen and Marburg Lung Center, 35392 Giessen, Germany.
Thuan DiepDepartment of Medicine, University of California San Diego, La Jolla, California 92093.
Shunhui ZhuangDepartment of Medicine, University of California San Diego, La Jolla, California 92093.
Thomas GawlowskiDepartment of Medicine, University of California San Diego, La Jolla, California 92093.
Ralph T SchermulyUniversity of Giessen and Marburg Lung Center, 35392 Giessen, Germany.
Alexander PfeiferInstitute for Pharmacology and Toxicology, University of Bonn, 53113 Bonn, Germany.
Gerry R BossDepartment of Medicine, University of California San Diego, La Jolla, California 92093.
Renate B PilzDepartment of Medicine, University of California San Diego, La Jolla, California 92093.
University of California, San Diego · USUniversity of Giessen · DEUniversity of Bonn · DE

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
REGULATION OF GENE EXPRESSION BY cGMP and PKG IN BONER01AR051300 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PILZ, RENATE B · 2004 to 2014
$3.1M
NIAMS NIH HHS R01 AR051300NIAMS NIH HHS R01-AR051300NINDS NIH HHS NS047101NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Pulmonary arterial hypertension (PAH) is a progressive, usually fatal disease with abnormal vascular remodeling. Pulmonary artery smooth muscle cells (PASMCs) from PAH patients are hyperproliferative and apoptosis-resistant and demonstrate decreased signaling in response to bone morphogenetic proteins (BMPs). Cyclic GMP-elevating agents are beneficial in PAH, but their mechanism(s) of action are incompletely understood. Here we show that BMP signaling via Smad1/5/8 requires cGMP-dependent protein kinase isotype I (PKGI) to maintain PASMCs in a differentiated, low proliferative state. BMP cooperation with cGMP/PKGI was crucial for transcription of contractile genes and suppression of pro-proliferative and anti-apoptotic genes. Lungs from mice with low or absent PKGI (Prkg1(+/-) and Prkg1(-/-) mice) exhibited impaired BMP signaling, decreased contractile gene expression, and abnormal vascular remodeling. Conversely, cGMP stimulation of PKGI restored defective BMP signaling in rats with hypoxia-induced PAH, consistent with cGMP-elevating agents reversing vascular remodeling in this PAH model. Our results provide a mechanism for the therapeutic effects of cGMP-elevating agents in PAH and suggest that combining them with BMP mimetics may provide a novel, disease-modifying approach to PAH therapy.

Indexed as

AnimalsCell Line, TransformedCyclic GMPCyclic GMP-Dependent Protein Kinase Type IHumansHypertension, PulmonaryMatrix Metalloproteinases, SecretedMiceMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleRatsSignal TransductionSmad ProteinsCyclic GMPCyclic GMP-Dependent Protein Kinase Type IMatrix Metalloproteinases, SecretedPRKG1 protein, humanPrkg1 protein, mousePrkg1 protein, ratSmad ProteinsBone Morphogenetic Protein (BMP)Cyclic GMP (cGMP)Protein Kinase G (PKG)Pulmonary HypertensionSmad Transcription Factor

Identifiers

PMID23612967
PMCPMC3675591
OpenAlexW2087928058

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.