Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37878711.
- Also identified by DOI 10.1126/sciadv.adj1019 and PMC identifier 10599623.
- Licence recorded as CC BY-NC.
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Abstract
While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either <i>Elane<sup>-/-</sup></i> or <i>Pad4<sup>-/-</sup></i> mice to generate NET-deficient diabetic mice. By 24 weeks of age, Akita aortae showed markedly impaired relaxation in response to acetylcholine, indicative of vascular dysfunction. Both Akita-<i>Elane<sup>-/-</sup></i> mice and Akita-<i>Pad4<sup>-/-</sup></i> mice had reduced levels of circulating NETs and improved acetylcholine-mediated aortic relaxation. Compared with wild-type aortae, the thromboxane metabolite TXB<sub>2</sub> was roughly 10-fold higher in both intact and endothelium-denuded aortae of Akita mice. In contrast, Akita-<i>Elane<sup>-/-</sup></i> and Akita-<i>Pad4<sup>-/-</sup></i> aortae had TXB<sub>2</sub> levels similar to wild type. In summary, inhibition of NETosis by two independent strategies prevented the development of vascular dysfunction in diabetic Akita mice. Thromboxane was up-regulated in the vessel walls of NETosis-competent diabetic mice, suggesting a role for neutrophils in driving the production of this vasoconstrictive and atherogenic prostanoid.
Medical subject headings
- Extracellular Traps
- Diabetes Mellitus, Experimental
- Diabetes Mellitus, Type 1