Evidence map›Paper›PMID 39462409›Full record

ArticleCardiovascular diabetology2024

Endothelial KLF11 is a novel protector against diabetic atherosclerosis.

Guizhen Zhao, Yang Zhao, Wenying Liang, Haocheng Lu, Hongyu Liu, Yongjie Deng, Tianqing Zhu, Yanhong Guo, Lin Chang, Minerva T Garcia-Barrio and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
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.

Guizhen ZhaoFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Yang ZhaoFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Wenying LiangDivision of Rheumatology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Haocheng LuSchool of Medicine, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China.
Hongyu LiuFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Yongjie DengFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Tianqing ZhuFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Yanhong GuoFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Lin ChangFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Minerva T Garcia-BarrioFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA.
Y Eugene ChenFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA. echenum@umich.edu.
Jifeng ZhangFrankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA. jifengz@umich.edu.

Funding

Development of phospholipid-based nanotherapeutics for treating abdominal aortic aneurysmR01HL165688 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Yanhong Guo, Anna Schwendeman · 2023 to 2026
$3.1M
Nitro-Fatty Acids and Cardiovascular DiseaseR01HL162294 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHEN, YUQING EUGENE, GARCIA-BARRIO, MINERVA T · 2022 to 2025
$2.9M
Vascular smooth muscle cell ferroptosis and abdominal aortic aneurysmR01HL166203 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Yanhong Guo · 2023 to 2026
$2.7M
Smooth muscle cell PRDM16 and aortic aneurysmR01HL151524 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHANG, LIN · 2021 to 2024
$2.7M
Kruppel-like factor 11 (KLF11) and atherosclerosisR01HL138139 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHANG, JIFENG · 2017 to 2021
$2.3M
Metaboloepigenetics and AtherosclerosisR01HL172832 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhen Zhao · 2024 to 2026
$1.8M
national institute of health HL151524national institute of health, united states HL172832NHLBI NIH HHS R01 HL138139NHLBI NIH HHS R01 HL151524NHLBI NIH HHS R01 HL162294NHLBI NIH HHS R01 HL165688NHLBI NIH HHS R01 HL166203NHLBI NIH HHS R01 HL172832NIH HHS HL138139NIH HHS HL162294
6 · The paper itself

Abstract

backgroundAtherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored.

methodsDiabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr

resultsWe found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure.

conclusionOur study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications.

Indexed as

AtherosclerosisEndothelial CellsMice, Inbred C57BLMice, KnockoutRepressor ProteinsAnimalsAortic DiseasesApoptosis Regulatory ProteinsBlood GlucoseCells, CulturedDiabetes Mellitus, ExperimentalDiabetic AngiopathiesDisease Models, AnimalEpithelial-Mesenchymal TransitionHumansHuman Umbilical Vein Endothelial CellsApoptosis Regulatory ProteinsBlood GlucoseKLF11 protein, humanKLF11 protein, mouseReceptors, LDLRepressor ProteinsAtherosclerosisDiabetesEndothelial cellEndothelial-to-mesenchymal transition (EndMT)KLF11

Identifiers

PMID39462409
PMCPMC11514907

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.