Evidence map›Paper›PMID 38853866›Full record

ArticlebioRxiv : the preprint server for biology2024

Branched chain α-ketoacids aerobically activate HIF1α signaling in vascular cells.

Wusheng Xiao, Nishith Shrimali, William M Oldham, Clary B Clish, Huamei He, Samantha J Wong, Bradley M Wertheim, Elena Arons, Marcia C Haigis, Jane A Leopold and 1 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Wusheng XiaoDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nishith ShrimaliDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7900-9099
William M OldhamDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-3029-4866
Clary B ClishBroad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.ORCID 0000-0001-8259-9245
Huamei HeDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Samantha J WongDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Bradley M WertheimDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1414-4692
Elena AronsDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Marcia C HaigisDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-2530-2681
Jane A LeopoldDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-0598-8882
Joseph LoscalzoDivisions of Cardiovascular Medicine and Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1153-8047

Funding

Pulmonary Hypertension Breakthrough InitiativeR24HL123767 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ALDRED, MICHEALA A, ERZURUM, SERPIL C. · 2014 to 2017
$10.1M
L-2-Hydroxyglutarate and Metabolic Remodeling in HypoxiaR01HL155107 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Joseph Loscalzo · 2021 to 2026
$4.1M
Branched-chain Keto-acids and Aerobic Glycolysis in Vascular Smooth Muscle CellsR01HL166137 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Joseph Loscalzo · 2023 to 2026
$2.8M
Investigating the role of PHD3 in lipid homeostasisR01DK127278 · NIDDK · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2021 to 2024
$1.7M
Personalized protein-protein interactomes and precision medicine in pulmonary arterial hypertensionR01HL155096 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI MARON, BRADLEY · 2021 to 2024
$1.6M
NHLBI NIH HHS R01 HL155096NHLBI NIH HHS R01 HL155107NHLBI NIH HHS R01 HL166137NHLBI NIH HHS R24 HL123767NIDDK NIH HHS R01 DK127278
6 · The paper itself

Abstract

Hypoxia-inducible factor 1α (HIF1α) is a master regulator of numerous biological processes under low oxygen tensions. Yet, the mechanisms and biological consequences of aerobic HIF1α activation by intrinsic factors, particularly in primary cells remain elusive. Here, we show that HIF1α signaling is activated in several human primary vascular cells under ambient oxygen tensions, and in vascular smooth muscle cells (VSMCs) of normal human lung tissue, which contributed to a relative resistance to further enhancement of glycolytic activity in hypoxia. Mechanistically, aerobic HIFα activation is mediated by paracrine secretion of three branched chain α-ketoacids (BCKAs), which suppress prolyl hydroxylase domain-containing protein 2 (PHD2) activity

Identifiers

PMID38853866
PMCPMC11160772

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.