Evidence mapPaperPMID 42269417Full record

ArticleAtherosclerosis2026

Context-dependent regulation of endothelial inflammation and atherosclerosis by endothelial microRNA-33.

Kathryn M Citrin, Yan Huang, Alex Ramos-Perez, Christian Castellanos, Alberto Canfrán-Duque, Xinbo Zhang, BalKrishna Chaube, Diego Sáenz de Urturi, Diego Gómez-Coronado, Stephania Libreros and 2 more

Abstract read
In one paragraph

Article in Atherosclerosis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Kathryn M CitrinVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT, USA.
Yan HuangVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Alex Ramos-PerezVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Christian CastellanosVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Alberto Canfrán-DuqueVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Xinbo ZhangVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
BalKrishna ChaubeVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Diego Sáenz de UrturiVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
Diego Gómez-CoronadoServicio Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
Stephania LibrerosVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University, New Haven, CT, USA.
Carlos Fernández-HernandoVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University, New Haven, CT, USA.
Yajaira SuárezVascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, USA; Yale Center for Molecular and System Metabolism, Yale University School of Medicine, New Haven, CT, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Pathology, Yale University, New Haven, CT, USA. Electronic address: yajaira.suarez@yale.edu.

Funding

Insights into the molecular mechanisms regulating vascular and immune metabolism in vascular diseasesR35HL155988 · NHLBI · YALE UNIVERSITY · 2022 to 2025
$3.9M
NHLBI NIH HHS R35 HL155988
6 · The paper itself

Abstract

BACKGROUND AND

aimsAtherosclerosis arises through the metabolic and inflammatory perturbation of numerous cells, including immune cells and endothelial cells (ECs). microRNA-33 (miR-33) regulates lipid metabolism and inflammatory responses of immune cells, but the impact of miR-33 on atherosclerosis progression has mixed effects, pointing to context- and cell-type-specific functions. Notably, the role of EC miR-33 in atherosclerosis remains unexplored, despite the central involvement of metabolic and inflammatory pathways in EC function. We sought to determine the definitive role of EC miR-33 in atherosclerosis progression.

methodsWe generated mice with an inducible EC-specific miR-33 knockout (iECKO), followed by PCSK9-AAV8 injection and western diet feeding. Detailed plaque analyses and scRNAseq were performed. For acute inflammation, we analyzed TNFα-mediated leukocyte recruitment in the air pouch model. In vitro approaches included the culture of human aortic ECs to analyze gene expression under inflammatory and lipid-laden conditions with miR-33 mimicry.

resultsiECKO mice showed accelerated lesion initiation, but this effect did not persist in advanced atherosclerosis, which is likely due to chronic hypercholesterolemia-driven downregulation of miR-33 that masks its deletion at later stages. Transcriptomic analyses revealed that cholesterol loading alters EC responses to inflammation, which can be partially rescued by miR-33 mimicry. Accordingly, iECKO mice exhibited heightened sensitivity to acute, normocholesterolemic inflammation, which is paralleled with regulation of E-selectin levels.

conclusionsOur work underscores the nuanced effects of miR-33 manipulation and highlights how well-described regulators of atherosclerosis progression may have unique cell type- and disease stage-dependent roles. Additionally, our work further implicates miR-33 as a regulator of EC function and identifies a new potential role in acute inflammation via E-selectin regulation.

Indexed as

Aortic DiseasesAtherosclerosisEndothelial CellsInflammationMicroRNAsAnimalsAortaCells, CulturedDisease Models, AnimalDisease ProgressionGene Expression RegulationHumansMaleMiceMice, Inbred C57BLMice, KnockoutMicroRNAsMIRN33a microRNA, humanMirn33 microRNA, mouseAtherosclerosisEndothelial cellInflammationmiRNA

Identifiers

PMID42269417
PMCPMC13312425

What Socratic holds

Textmetadata
LicenceTDM
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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.