Evidence mapPaperPMID 39934897Full record

ArticleCardio-oncology (London, England)2025

Acute vascular and cardiac effects of lenvatinib in mice.

Dustin N Krüger, Patrizia Pannucci, Callan D Wesley, Cedric H G Neutel, Wim Martinet, Guido R Y De Meyer, Stephen J Hill, Jeanette Woolard, Constantijn Franssen, Pieter-Jan Guns

Abstract read
In one paragraph

Article in Cardio-oncology (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
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 synthesis or guideline pooled it.

  1. Pooled it
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

10 authors.

Dustin N Krüger *Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium. dustin.kruger@uantwerpen.be.
Patrizia Pannucci *Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK.
Callan D WesleyLaboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium.
Cedric H G NeutelLaboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium.
Wim MartinetLaboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium.
Guido R Y De MeyerLaboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium.
Stephen J HillDivision of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK.
Jeanette Woolard *Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK.
Constantijn Franssen *Research Group Cardiovascular Diseases, University of Antwerp, Antwerp, B-2610, Belgium.
Pieter-Jan Guns *Laboratory of Physiopharmacology, Faculty of Medicine and Health Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, Antwerp, B-2610, Belgium.

Funding

Belgian Foundation against Cancer 2021-034Belgian Foundation against Cancer C/2020/1374Bijzonder Onderzoeksfonds UAntwerp,Belgium 49194Bijzonder Onderzoeksfonds UGent 49195DOCPRO4 - Antwerp, Belgium 39984Horizon 2020 858070King Baudouin Foundation, Belgium Funds Pierre Masure, Alphonse & Marie Walckiers, and De Winter-Vermant 2018Research Foundation - Flanders, Belgium I005122N
6 · The paper itself

Abstract

backgroundTyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) receptor signalling are used in cancer therapy to inhibit angiogenesis. Unfortunately, VEGF inhibitors are known to induce severe hypertension in patients. This study aimed to elucidate the impact of the TKI lenvatinib on blood pressure, arterial stiffness, vascular reactivity, as well as cardiac function in a short-term murine model to shed light on potential contributors to cardiovascular (CV) toxicities associated with VEGF inhibition.

methodsMale C57BL/6J mice were randomly divided into 2 cohorts, either treated for 4 days with lenvatinib 4 mg/kg/day or 40% hydroxypropyl β-cyclodextrin as control. In an additional study, mice were subjected to a 4-day treatment followed by a 4-day wash-out, with echocardiography and blood pressure measurements performed on day 2 and 7. Subsequently, ex vivo vascular reactivity of thoracic aortic segments was determined.

resultsLenvatinib induced hypertension and arterial stiffness (i.e., increased pulse wave velocity), starting from day 2 of treatment. Further, left ventricular ejection fraction was reduced and the ventricle dilated upon treatment. Lenvatinib induced neither endothelial dysfunction nor impaired vascular smooth muscle cell reactivity to nitric oxide (NO). Interestingly, lenvatinib demonstrated a concentration-dependent increase in ATP-mediated relaxation. In addition, after the 4-day wash-out period, lenvatinib-treated mice did not show complete remission of hypertension. However, arterial stiffness, ATP-mediated relaxation and cardiac adaptation were recovered.

conclusionThis comprehensive investigation provides valuable insights into the interplay between VEGF inhibition, vascular function and cardiac outcomes, emphasising the need for nuanced understanding and further exploration of the differential effects of lenvatinib on the CV system. Additionally, the study proposes a synergistic formation between VEGF and ATP, indicating an enhanced response via P2Yx receptor signalling.

Indexed as

ATPCardiovascular toxicityHypertensionLenvatinibTKIsVEGFR

Identifiers

PMID39934897
PMCPMC11816767

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.