Endothelial Senescence Drives Deleterious Endothelial-Adipocyte Cross-Talk in Patients With Heart Failure and Type 2 Diabetes

Abstract

Subcutaneous adipose tissue microvascular endothelial cells (MVECs) from patients with type 2 diabetes mellitus and heart failure exhibit a senescent phenotype characterized by elevated senescence-associated secretory phenotype markers, reduced adenosine triphosphate production, and impaired angiogenic and proliferative capacities. When cocultured with healthy adipocytes, senescent MVECs drive adverse cross-talk, inducing a proinflammatory adipocyte phenotype with increased interleukin-6 expression and reduced glucose uptake. Digoxin reduces MVEC senescence and restores healthy cross-talk, improving glucose uptake and mitigating the effects of senescent MVECs on adipocytes.

Metadata

Item Type:	Article
Authors/Creators:	Brown, O.I. Bridge, K.I. Bruns, A.-F. Luk, C. Makava, N. Cheng, C.W. Wijayagoonawardana, P. Tayebjee, M. Saunderson, C.E.D. Straw, S. Drozd, M. https://orcid.org/0000-0003-0255-4624 Skroma, A. Haywood, N.J. Viswambharan, H. https://orcid.org/0000-0002-7616-5026 Kamalathasan, S. Gierula, J. https://orcid.org/0000-0001-9588-191X Beech, D.J. https://orcid.org/0000-0002-7683-9422 Naseem, K. Griffin, K.J. Wheatcroft, S.B. https://orcid.org/0000-0002-6741-9012 Witte, K.K. https://orcid.org/0000-0002-7146-7105 Roberts, L.D. Cubbon, R.M. https://orcid.org/0000-0001-7844-3600 Kearney, M.T. https://orcid.org/0000-0002-9376-8814
Copyright, Publisher and Additional Information:	© 2026, The Authors. Published by Elsevier on Behalf of The American College of Cardiology Foundation. This is an Open Access Article under the CC BY License (http://creativecommons.org/licenses/by/4.0/).
Keywords:	cell cross-talk; endothelium; heart failure; senescence; type 2 diabetes mellitus
Dates:	Accepted: 24 February 2026 Published (online): 13 April 2026 Published: 1 May 2026
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Medicine & Health Faculty Office (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds)
Funding Information:	Funder Grant number British Heart Foundation Accounts Payable - Gloria Sankey CH/13/1/30086
Date Deposited:	24 Apr 2026 13:35
Last Modified:	24 Apr 2026 13:35
Status:	Published
Publisher:	Elsevier
Identification Number:	10.1016/j.jacbts.2026.101527
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:240409

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Endothelial Senescence Drives Deleterious Endothelial-Adipocyte Cross-Talk in Patients With Heart Failure and Type 2 Diabetes

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