ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026
Wound Healing and Angiogenic Profiling of Dermal Endothelial Cells Isolated From People With Type 2 Diabetes.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Impaired wound healing in type 2 diabetes (T2D) is associated with microvascular dysfunction and remains a significant clinical challenge. We aimed to determine whether primary human dermal microvascular endothelial cells (HDMVECs) from individuals with T2D exhibit abnormal cellular functions, and whether exposure to T2D serum impacts healthy endothelial function. In Experiment 1, T2D-HDMVECs displayed paradoxically higher migratory and angiogenic capacities than their healthy counterparts, despite markedly reduced eNOS expression and disrupted endothelial-identity gene expression. In Experiments 2 and 3, healthy HDMVECs showed decreased tube formation, nitric oxide production, and Notch/angiogenesis-related gene expression after exposure to both healthy and T2D serum, suggesting the presence of serum-derived factors that suppress these pathways. However, T2D-HDMVECs remained largely unresponsive to these serum-driven effects, reinforcing an intrinsic reprogramming of T2D endothelial cells. Additional analyses revealed selective alterations in redox and angiogenic signaling pathways (e.g., NOX4, FLT1), whereas canonical regulators such as VEGFA and PFKB3 were not affected by serum exposure. Overall, our data reveal a complex interplay between cell-autonomous alterations and extrinsic signals in diabetic endothelial dysfunction. Therapeutic strategies targeting both intrinsic cellular programs (e.g., eNOS, Notch signaling) and the circulating milieu may represent promising avenues for enhancing wound repair in patients with T2D.
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