Evidence map›Paper›PMID 41026534›Full record

ArticleJCI insight2025

Characterization of anticancer therapy-induced microvascular dysfunction in patients with breast cancer supports targeted intervention.

Janée D Terwoord, Laura E Norwood Toro, Shelby N Hader, Stephen T Hammond, Joseph C Hockenberry, Jasmine Linn, Ibrahim Y Vazirabad, Amanda L Kong, Alison J Kriegel, Ziqing Liu and 4 more

Abstract read
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

14 authors.

Janée D TerwoordCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Laura E Norwood ToroCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Shelby N HaderCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Stephen T HammondCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Joseph C HockenberryCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Jasmine LinnCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Ibrahim Y VazirabadDepartment of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Amanda L KongDepartment of Surgery, Froedtert and Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Alison J KriegelCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Ziqing LiuCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Riikka M KiveläWihuri Research Institute and Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Gillian MurtaghCore Diagnostics, Abbott Laboratories, Abbott Park, Illinois, USA.
David D GuttermanCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Andreas M BeyerCardiovascular Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Funding

Training in Signature Transdisciplinary Cardiovascular SciencesT32HL134643 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Justin L Grobe, Jacquelyn P Kulinski · 2017 to 2026
$4.2M
Pivotal Role of Mitochondrial Telomerase in Regulation of Vascular Tone and Redox HomeostasisR01HL133029 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI BEYER, ANDREAS M · 2017 to 2021
$2.2M
Mechanism of Chemotherapy Induced Microvascular Dysfunction in Cancer SurvivorsR01HL173549 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI Andreas M Beyer · 2024 to 2026
$2.1M
NHLBI NIH HHS R01 HL133029NHLBI NIH HHS R01 HL173549NHLBI NIH HHS T32 HL134643
6 · The paper itself

Abstract

BACKGROUNDCardiotoxicity is a major complication of anticancer therapy (CTx); however, the effect of CTx on the microcirculation is not well defined. This study evaluated the effect of CTx on microvascular function in patients with breast cancer (PwBC).METHODSEndothelial function and angiogenic potential were assessed in arterioles and adipose biopsies obtained from PwBC undergoing CTx (longitudinal and cross-sectional) and in healthy arterioles exposed to doxorubicin (Dox), trastuzumab (TZM), or paclitaxel (PTX) ex vivo. VEGF-B protein was used to test feasibility of targeted intervention.RESULTSPwBC treated with Dox and/or TZM developed profound microvascular endothelial dysfunction that persisted for ≥ 9 months after treatment cessation. Angiogenic potential was reduced during CTx and recovered within 1 month. Gene expression related to angiogenesis and inflammation changed over the course of clinical treatment. Adipose arterioles from healthy donors developed endothelial dysfunction when exposed to Dox or TZM ex vivo. PTX, which poses minimal cardiovascular risk, had no effect on vasomotor function. Ex vivo exposure to Dox or PTX suppressed angiogenic potential, whereas TZM had no effect. VEGF-B protein preserved endothelial function in arterioles exposed to Dox or TZM ex vivo.CONCLUSIONPwBC undergoing treatment with Dox and/or TZM develop prolonged microvascular endothelial dysfunction that is recapitulated in healthy arterioles exposed to Dox or TZM ex vivo. Targeted intervention with VEGF-B protects against direct Dox- or TZM-induced vascular toxicity in human arterioles ex vivo.FUNDINGNIH, American Heart Association, WeCare Foundation, Medical College of Wisconsin, Advancing a Healthier Wisconsin, Jenny and Antti Wihuri Foundation.

Indexed as

Antineoplastic AgentsBreast NeoplasmsMicrocirculationMicrovesselsAdipose TissueAdultAgedArteriolesCross-Sectional StudiesDoxorubicinEndothelium, VascularFemaleHumansMiddle AgedNeovascularization, PathologicPaclitaxelAntineoplastic AgentsDoxorubicinPaclitaxelTrastuzumabBreast cancerCardiologyEndothelial cellsMicrocirculationOncologyVascular biology

Identifiers

PMID41026534
PMCPMC12643535

What OpenQuestion holds

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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 OpenQuestion graph.