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.