Evidence map›Paper›PMID 28935506›Full record

ArticleJournal of molecular and cellular cardiology2017

Endothelial specific SIRT3 deletion impairs glycolysis and angiogenesis and causes diastolic dysfunction.

Xiaochen He, Heng Zeng, Sean T Chen, Richard J Roman, Judy L Aschner, Sean Didion, Jian-Xiong Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular and cellular cardiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
3.9field-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

79 citing papers in PubMed, 125 citations in OpenAlex.

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  20. TIGAR Deficiency Blunts Angiotensin-II-Induced Cardiac Hypertrophy in Mice.International journal of molecular sciences · 2024
    Article

19 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

Xiaochen HeDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Heng ZengDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Sean T ChenDuke University School of Medicine, Durham, NC, USA.
Richard J RomanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Judy L AschnerDepartment of Pediatrics, Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, NY, USA.
Sean DidionDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Jian-Xiong ChenDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, USA. Electronic address: JChen3@umc.edu.
University of Mississippi Medical Center · USChildren's Hospital at Montefiore · USDuke University · US

Funding

Regulation of vascular maturation/regression in diabetesR01HL102042 · NHLBI · VANDERBILT UNIVERSITY · PI CHEN, JIAN-XIONG · 2010 to 2020
$3.0M
Molecular Mechanisms of Hypertension in the MicrocirculationR01HL107632 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI DIDION, SEAN P · 2011 to 2014
$1.5M
NHLBI NIH HHS R01 HL102042NHLBI NIH HHS R01 HL107632
6 · The paper itself

Abstract

Endothelial glycolysis plays a critical role in the regulation of angiogenesis. We investigated the role of Sirtuin 3 (SIRT3) on endothelial cell (EC) glycolytic metabolism, angiogenesis, and diastolic function. Our aim was to test the hypothesis that loss of SIRT3 in ECs impairs endothelial glycolytic metabolism and angiogenesis and contributes to myocardial capillary rarefaction and the development of diastolic dysfunction. Using SIRT3 deficient ECs, SIRT3 was found to regulate a metabolic switch between mitochondrial respiration and glycolysis. SIRT3 knockout (KO)-ECs exhibited higher mitochondrial respiration and reactive oxygen species (ROS) formation. SIRT3 knockout (KO)-ECs exhibited a reduction in the expression of glycolytic enzyme, PFKFB3, and a fall in glycolysis and angiogenesis. Blockade of PFKFB3 reduced glycolysis and downregulated expression of VEGF and Angiopoietin-1 (Ang-1) in ECs. Deletion of SIRT3 in ECs also impaired hypoxia-induced expression of HIF-2α, VEGF, and Ang-1, as well as reduced angiogenesis. In vivo, endothelial-specific SIRT3 KO (ECKO) mice exhibited a myocardial capillary rarefaction together with a reduced coronary flow reserve (CFR) and diastolic dysfunction. Histologic study further demonstrated that knockout of SIRT3 in ECs significantly increased perivascular fibrosis in the coronary artery. These results implicate a role of SIRT3 in modulating endothelial function and cardiac function. Ablation of SIRT3 leads to impairment of EC glycolytic metabolism and angiogenic signaling, which may contribute to coronary microvascular rarefaction and diastolic dysfunction in SIRT3 ECKO mice.

Indexed as

DiastoleGene DeletionGlycolysisNeovascularization, PhysiologicAnimalsCapillariesCell HypoxiaCoronary CirculationEndothelial CellsHeartHeart FailureMice, KnockoutModels, BiologicalOrgan SpecificityOxygen ConsumptionPhenotypePFKFB3 protein, mousePhosphofructokinase-2Sirtuin 3Coronary microvascular dysfunctionDiastolic dysfunctionMetabolic reprogramPFKFB3SIRT3

Identifiers

PMID28935506
PMCPMC5647246
OpenAlexW2758776248

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.