Evidence map›Paper›PMID 35899624›Full record

ArticleCirculation research2022

Endothelial UCP2 Is a Mechanosensitive Suppressor of Atherosclerosis.

Jiang-Yun Luo, Chak Kwong Cheng, Lei He, Yujie Pu, Yang Zhang, Xiao Lin, Aimin Xu, Chi Wai Lau, Xiao Yu Tian, Ronald Ching Wan Ma and 2 more

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

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.0field-weighted citation impact, top 3% 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

54 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
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  5. Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  14. Deciphering Uncoupling Proteins in Cellular Homeostasis and Metabolic Health.International journal of biological sciences · 2026
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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

12 authors at 7 institutions in 4 countries.

Jiang-Yun Luo *Institute for Cardiovascular Development and Regenerative Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China (J.-Y.L.).ORCID 0000-0002-9087-227X
Chak Kwong Cheng *Heart and Vascular Institute, Shenzhen Research Institute and School of Biomedical Sciences (J.-Y.L., C.K.C., L.H., Y.P., C.W.L., X.Y.T.), Chinese University of Hong Kong, China.
Lei HeHeart and Vascular Institute, Shenzhen Research Institute and School of Biomedical Sciences (J.-Y.L., C.K.C., L.H., Y.P., C.W.L., X.Y.T.), Chinese University of Hong Kong, China.
Yujie PuHeart and Vascular Institute, Shenzhen Research Institute and School of Biomedical Sciences (J.-Y.L., C.K.C., L.H., Y.P., C.W.L., X.Y.T.), Chinese University of Hong Kong, China.
Yang ZhangSchool of Public Health (Shenzhen), Sun Yat-sen University, Guangdong, China (Y.Z.).
Xiao LinSchool of Life Sciences (X.L.), Chinese University of Hong Kong, China.ORCID 0000-0002-2559-2343
Aimin XuState Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, The University of Hong Kong, China (A.X.).
Chi Wai LauHeart and Vascular Institute, Shenzhen Research Institute and School of Biomedical Sciences (J.-Y.L., C.K.C., L.H., Y.P., C.W.L., X.Y.T.), Chinese University of Hong Kong, China.
Xiao Yu TianHeart and Vascular Institute, Shenzhen Research Institute and School of Biomedical Sciences (J.-Y.L., C.K.C., L.H., Y.P., C.W.L., X.Y.T.), Chinese University of Hong Kong, China.ORCID 0000-0003-3472-9898
Ronald Ching Wan MaDepartment of Medicine and Therapeutics (R.C.W.M.), Chinese University of Hong Kong, China.
Hanjoong JoWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (H.J.).ORCID 0000-0003-1833-372X
Yu HuangDepartment of Biomedical Sciences, City University of Hong Kong, China (C.K.C., L.H., Y.P., Y.H.).ORCID 0000-0002-1277-6784
City University of Hong Kong · HKChinese University of Hong Kong · HKChinese University of Hong Kong, Shenzhen · CNPharmaceutical Biotechnology (Czechia) · CZSun Yat-sen University · CNThe Wallace H. Coulter Department of Biomedical Engineering · USXinHua Hospital · CN

Funding

Shear stress, endothelial miRNAs, and AV calcificationR01HL119798 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG, YOGANATHAN, AJIT P · 2013 to 2022
$4.7M
HEG1 in endothelial function and atherosclerosisR01HL158571 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2021 to 2024
$2.7M
Role of flow-sensitive KLK10 in endothelial dysfunction and atherosclerosisR01HL139757 · NHLBI · EMORY UNIVERSITY · PI JO, HANJOONG · 2018 to 2021
$1.6M
NHLBI NIH HHS R01 HL119798NHLBI NIH HHS R01 HL139757NHLBI NIH HHS R01 HL158571
6 · The paper itself

Abstract

backgroundInflamed endothelial cells (ECs) trigger atherogenesis, especially at arterial regions experiencing disturbed blood flow. UCP2 (Uncoupling protein 2), a key mitochondrial antioxidant protein, improves endothelium-dependent relaxation in obese mice. However, whether UCP2 can be regulated by shear flow is unknown, and the role of endothelial UCP2 in regulating inflammation and atherosclerosis remains unclear. This study aims to investigate the mechanoregulation of UCP2 expression in ECs and the effect of UCP2 on endothelial inflammation and atherogenesis.

methodsIn vitro shear stress simulation system was used to investigate the regulation of UCP2 expression by shear flow. EC-specific Ucp2 knockout mice were used to investigate the role of UCP2 in flow-associated atherosclerosis.

resultsShear stress experiments showed that KLF2 (Krüppel-like factor 2) mediates fluid shear stress-dependent regulation of UCP2 expression in human aortic and human umbilical vein ECs. Unidirectional shear stress, statins, and resveratrol upregulate whereas oscillatory shear stress and proinflammatory stimuli inhibit UCP2 expression through altered KLF2 expression. KLF2 directly binds to UCP2 promoter to upregulate its transcription in human umbilical vein ECs. UCP2 knockdown induced expression of genes involved in proinflammatory and profibrotic signaling, resulting in a proatherogenic endothelial phenotype. EC-specific

conclusionsAltogether, our studies uncover that UCP2 is novel mechanosensitive gene under the control of fluid shear stress and KLF2 in ECs. UCP2 expression is critical for endothelial proinflammatory response and atherogenesis. Therapeutic strategies enhancing UCP2 level may have therapeutic potential against atherosclerosis.

Indexed as

AtherosclerosisPlaque, AtheroscleroticAnimalsCells, CulturedEndotheliumHumansHuman Umbilical Vein Endothelial CellsInflammationKruppel-Like Transcription FactorsMiceStress, MechanicalUncoupling Protein 2Kruppel-Like Transcription FactorsUCP2 protein, humanUcp2 protein, mouseUncoupling Protein 2antioxidantsatherosclerosisendothelial cellinflammationresveratrol

Identifiers

PMID35899624
PMCPMC9390236
OpenAlexW4288080647

What OpenQuestion holds

Textmetadata
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.