| First Author | Liu C | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 43 | Pages | eadj1019 |
| PubMed ID | 37878711 | Mgi Jnum | J:342212 |
| Mgi Id | MGI:7546433 | Doi | 10.1126/sciadv.adj1019 |
| Citation | Liu C, et al. (2023) Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice. Sci Adv 9(43):eadj1019 |
| abstractText | 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 Elane(-/-) or Pad4(-/-) 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-Elane(-/-) mice and Akita-Pad4(-/-) mice had reduced levels of circulating NETs and improved acetylcholine-mediated aortic relaxation. Compared with wild-type aortae, the thromboxane metabolite TXB(2) was roughly 10-fold higher in both intact and endothelium-denuded aortae of Akita mice. In contrast, Akita-Elane(-/-) and Akita-Pad4(-/-) aortae had TXB(2) 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. |
