Evidence map›Paper›PMID 40899274›Full record

ArticleCirculation research2025

Single-Short Partial Reprogramming of the Endothelial Cells Decreases Blood Pressure via Attenuation of EndMT in Hypertensive Mice.

Laena Pernomian, Emily W Waigi, Vi Nguyen, Ahmed D Mohammed, Tiago J Costa, Milene T Fontes, Jason L Kubinak, Andrew V Aitken, Vinicia Campana Biancardi, Kamryn Gleason and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Progranulin deficiency induces premature vascular senescence and dysfunction.American journal of physiology. Heart and circulatory physiology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Laena PernomianDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0003-3930-0919
Emily W WaigiDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.
Vi NguyenDepartment of Cell Biology and Anatomy (L.P., E.W.W., V.N., T.J.C., M.T.F., C.G.M., W.T., C.F.W.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0002-0688-0286
Ahmed D MohammedDepartment of Pathology, Microbiology and Immunology (A.D.M., J.L.K.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0002-2504-8583
Tiago J CostaDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.
Milene T FontesDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.
Jason L KubinakDepartment of Pathology, Microbiology and Immunology (A.D.M., J.L.K.), School of Medicine Columbia, University of South Carolina.
Andrew V AitkenDepartment of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, AL (A.V.A., V.C.B.).ORCID 0000-0001-9229-9369
Vinicia Campana BiancardiDepartment of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, AL (A.V.A., V.C.B.).ORCID 0000-0001-7301-1702
Kamryn GleasonDepartment of Biomedical Engineering Program, University of South Carolina, Columbia (K.G., T.S., C.G.M., C.F.W.).
Tarek ShazlyDepartment of Biomedical Engineering Program, University of South Carolina, Columbia (K.G., T.S., C.G.M., C.F.W.).
David A SinclairDepartment of Genetics, Paul F. Glenn Center for Biology of Aging Research, Blavatnik Institute, Harvard Medical School, Boston, MA (D.A.S.).ORCID 0000-0002-9936-436X
Cameron G McCarthyDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0002-1380-779X
Yunguan WangDepartment of Pediatrics, University of Cincinnati College of Medicine, OH (Y.W.).ORCID 0000-0003-0767-6188
Wenbin TanDepartment of Cell Biology and Anatomy (L.P., E.W.W., V.N., T.J.C., M.T.F., C.G.M., W.T., C.F.W.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0002-2334-8988
Camilla Ferreira WenceslauDepartment of Cell Biology and Anatomy, Cardiovascular Translational Research Center (L.P., E.W.W., T.J.C., M.T.F., C.G.M., C.F.W.), School of Medicine Columbia, University of South Carolina.ORCID 0000-0002-0815-3568

Funding

South Carolina IDeA Networks of Biomedical Research (SC INBRE V)P20GM103499 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI EDIE C GOLDSMITH · 2012 to 2026
$61.0M
Formyl peptide receptor activation induces vascular plasticity and remodeling inhypertensionR01HL149762 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI WENCESLAU, CAMILLA FERREIRA · 2021 to 2025
$1.9M
Vascular Pathogenesis of Port Wine StainR01AR073172 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI TAN, WENBIN · 2018 to 2022
$1.5M
Intrarenal Arteries Sense N-formyl Peptides Leading to Vascular Injury in SepsisR00GM118885 · NIGMS · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI WENCESLAU, CAMILLA FERREIRA · 2019 to 2021
$746k
Autophagy regulates β-hydroxybutyrate synthesis to prevent hypertension-associated premature vascular agingR00HL151889 · NHLBI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI MCCARTHY, CAMERON · 2022 to 2024
$742k
BD FACSymphony A5 Cell AnalyzerS10OD032271 · OD · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI KUBINAK, JASON L, PRICE, ROBERT L · 2022 to 2022
$513k
Reprogramming endothelial cells to prevent and treat Alzheimer disease (AD) and HypertensionR21AG085331 · NIA · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI WENCESLAU, CAMILLA FERREIRA · 2024 to 2025
$410k
Generation and Validation of Disease Models for Port-Wine BirthmarksR21AR083066 · NIAMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI TAN, WENBIN · 2023 to 2024
$356k
NHLBI NIH HHS R00 HL151889NHLBI NIH HHS R01 HL149762NIAMS NIH HHS R01 AR073172NIAMS NIH HHS R21 AR083066NIA NIH HHS R21 AG085331NIGMS NIH HHS P20 GM103499NIGMS NIH HHS R00 GM118885NIH HHS S10 OD032271
6 · The paper itself

Abstract

backgroundSmall artery remodeling and endothelial dysfunction are hallmarks of hypertension. Evidence supports a likely causal association between cardiovascular diseases and endothelial-to-mesenchymal transition (EndMT), a cellular transdifferentiation process in which endothelial cells (ECs) partially lose their identity and acquire mesenchymal phenotypes. EC reprogramming represents an innovative strategy in regenerative medicine to prevent deleterious effects induced by cardiovascular diseases.

methodsUsing partial reprogramming of ECs, via overexpression of Oct-3/4-Sox-2-Klf-4 (OSK) transcription factors, we aimed to bring ECs back to a youthful phenotype in hypertension. Primary ECs were infected with lentiviral vectors (LVs) containing the specific EC promoter Cdh5 (cadherin-5) and the reporter EGFP (enhanced green fluorescent protein) with empty vector (LV control) or LV with Oct-3/4-Sox-2-Klf-4. Confocal microscopy and Western blotting analysis were used to confirm OSK overexpression. Cellular migration, senescence, and apoptosis were evaluated. Human aortic ECs from normotensive patients and patients with hypertension were analyzed after OSK treatments for eNOS (endothelial nitric oxide synthase), nitric oxide (NO), and genetic profile. Male and female normotensive (BPN/3J or blood pressure normal mouse strain) and hypertensive (BPH/2J or blood pressure high mouse strain) mice were treated with LV control or LV with Oct-3/4-Sox-2-Klf-4 and evaluated 10 days post-infection. The blood pressure, cardiac function, vascular reactivity of small arteries, and EndMT inhibition were analyzed.

resultsOSK overexpression induced partial EC reprogramming in vitro, and these cells had lower migratory capability. OSK treatment of BPH/2J mice reduced blood pressure and resistance arteries hypercontractility, via the attenuation of endothelial-to-mesenchymal transition and elastin breaks. EGFP was detected in vivo in the prefrontal cortex. OSK-treated hypertensive human aortic ECs showed high eNOS activation and NO production, with low reactive oxygen species (ROS) formation. Single-cell RNA analysis showed that OSK alleviated EC senescence and EndMT, restoring their phenotypes in human aortic ECs from patients with hypertension.

conclusionsOverall, these data indicate that OSK treatment and EC reprogramming can decrease blood pressure and reverse hypertension-induced vascular damage.

Indexed as

Blood PressureCellular ReprogrammingEndothelial CellsEpithelial-Mesenchymal TransitionHypertensionAnimalsAntigens, CDCadherin 5CadherinsCell MovementCells, CulturedCell TransdifferentiationDisease Models, AnimalEndothelial-Mesenchymal TransitionFemaleHumansAntigens, CDCadherin 5CadherinsKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsNitric Oxide Synthase Type IIIOctamer Transcription Factor-3SOXB1 Transcription Factorsblood pressurecardiovascular diseasesendothelial progenitor cellshypertensionvascular remodeling

Identifiers

PMID40899274
PMCPMC12530109

What Socratic 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 Socratic graph.