Evidence mapPaperPMID 41385115Full record

ArticleAngiogenesis2025

Sex-specific angiogenic responses in endothelial cells-role of the pluripotency factor OCT4.

Junchul Shin, Junyoung Hong, Iuliia Molokotina, Irene Krukovets, Ellin Kim, Svyatoslav Tkachenko, Eugene Podrez, Tatiana V Byzova, Olga A Cherepanova

Abstract read
In one paragraph

Article in Angiogenesis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

9 authors.

Junchul Shin *Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, OH, USA.
Junyoung Hong *Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, OH, USA.
Iuliia MolokotinaDepartment of Neurosciences, Cleveland Clinic, Cleveland, OH, USA.
Irene KrukovetsDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, OH, USA.
Ellin KimDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, OH, USA.
Svyatoslav TkachenkoDepartment of Pathology & Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Eugene PodrezDepartment of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA.
Tatiana V ByzovaDepartment of Neurosciences, Cleveland Clinic, Cleveland, OH, USA.
Olga A CherepanovaDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, OH, USA. cherepol@ccf.org.

Funding

Role of TLR2 in angiogenesisR01HL145536 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2019 to 2022
$2.6M
Novel oxidative pathway targets microglia in Alzheimer's diseaseR01AG082382 · NIA · CLEVELAND CLINIC LERNER COM-CWRU · PI Tatiana V Byzova, EUGENE A PODREZ · 2024 to 2026
$2.3M
Role of the TLR4 signaling in smooth muscle cell phenotypic transitionR01HL150193 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI CHEREPANOVA, OLGA · 2021 to 2024
$1.6M
NHLBI NIH HHS R01 HL145536NHLBI NIH HHS R01 HL150193NIA NIH HHS R01 AG082382NIH HHS R01HL150193
6 · The paper itself

Abstract

The study investigates the sex-specific effects of the pluripotency factor OCT4 deficiency in endothelial cells (ECs) on angiogenesis. OCT4 is known for its role in embryonic stem cells, but we recently found that it plays a protective role in ECs during atherosclerosis. Herein, we utilized cultured mouse aortic ECs (MAECs) and several in vivo models, including skin wounding, melanoma tumor implantation, and hindlimb ischemia, to explore the role of OCT4 in angiogenesis in both male and female mice. Our findings revealed significant sexual dimorphism in wild type mice, along with sex differences in responses to OCT4 deficiency across all three in vivo models. Male mice with endothelial Oct4 knockout had faster skin wound healing, increased vascularization, and quicker blood flow recovery after hindlimb ischemia than wild-type mice. In contrast, female mice with endothelial Oct4 knockout experienced delayed wound healing, no significant change in blood flow recovery after hindlimb ischemia, and increased tumor growth. Mechanistically, MCP1, a key angiogenic chemokine, was differentially regulated in male and female Oct4 knockout compared to wild-type MAECs, suggesting OCT4-dependent regulation of MCP1 as a critical mechanism for sex differences in angiogenic responses. RNA sequencing (RNAseq) analysis revealed distinct gene expression profiles in male and female MAECs upon OCT4 deficiency. Notably, female ECs exhibited upregulation of pro-inflammatory genes, which, although modest relative to their already elevated baseline, may contribute to the enhanced tumor growth observed in mutant females. In contrast, male ECs exhibited increased expression of cell cycle- and angiogenesis-related genes, correlating with their enhanced angiogenic responses. Overall, the research provides novel insights into the sex-specific functional role of OCT4 in ECs during angiogenesis and emphasizes the need for developing sex-specific EC-targeting therapeutic strategies for cardiovascular diseases and cancer.

Indexed as

Endothelial CellsNeovascularization, PathologicNeovascularization, PhysiologicOctamer Transcription Factor-3Sex CharacteristicsAnimalsChemokine CCL2FemaleHindlimbIschemiaMaleMiceMice, Inbred C57BLMice, KnockoutWound HealingChemokine CCL2Octamer Transcription Factor-3Pou5f1 protein, mouseAngiogenesisEndothelial cellsOCT4Sex differences

Identifiers

PMID41385115
PMCPMC12700951

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 Socratic graph.