Endothelial Senescence Drives Deleterious Endothelial-Adipocyte Cross-Talk in Patients With Heart Failure and Type 2 Diabetes
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.
Authors
- Hema Viswambharan (ORCID: https://orcid.org/0000-0002-7616-5026)
- Pradeep Wijayagoonawardana (ORCID: https://orcid.org/0000-0002-2846-4443)
- John Gierula (ORCID: https://orcid.org/0000-0001-9588-191X)
- Muzahir H. Tayebjee (ORCID: https://orcid.org/0000-0002-9591-3691)
- David J. Beech (ORCID: https://orcid.org/0000-0002-7683-9422)
- Katherine Bridge (ORCID: https://orcid.org/0000-0003-0495-9465)
- Natalie J Haywood (ORCID: https://orcid.org/0000-0002-8762-7257)
- Michael Drozd (ORCID: https://orcid.org/0000-0003-0255-4624)
- Oliver Brown (ORCID: https://orcid.org/0000-0001-7555-476X)
- Lee D. Roberts (ORCID: https://orcid.org/0000-0002-1455-5248)
- Richard M. Cubbon (ORCID: https://orcid.org/0000-0001-7844-3600)
- Stephe Kamalathasan (ORCID: https://orcid.org/0000-0002-9813-3885)
- Cheukyau Luk (ORCID: https://orcid.org/0000-0002-6828-5423)
- Kathryn J Griffin (ORCID: https://orcid.org/0000-0002-3154-3273)
- Natallia Makava
- Anna Skroma
- Stephen B. Wheatcroft
- Sam Straw
- Klaus K. Witte
- Christopher E.D. Saunderson
- Mark T. Kearney
- Alexander-Francisco Bruns
- Khalid Naseem
- Chew W. Cheng
Institutions
- University of Leeds (GB)
- Leeds Teaching Hospitals NHS Trust (GB)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2026-04-11
- DOI
- https://doi.org/10.1016/j.jacbts.2026.101527
- Primary Topic
- Telomeres, Telomerase, and Senescence
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- British Heart Foundation