Mills William A, Savory Niesha A, Lopez-Ortiz Aida Oryza, Lentferink Dennis H, González Ibáñez Fernando, Agochi Praise, Rastegar Elina, Gupta Arnav, Gupta Deetya, Suram Arya, Isakson Brant E, Tremblay Marie-Ève, Eyo Ukpong B
Department of Neuroscience, University of Virginia School of Medicine, Charlottesville, VA, USA.
Brain, Immunology, & Glia Center, University of Virginia School of Medicine, Charlottesville, VA, USA.
Nat Commun. 2025 Jul 1;16(1):5704. doi: 10.1038/s41467-025-60753-x.
Microglia and border associated macrophages have been implicated in hypercapnia, but it is unknown which myeloid cell modulates which vessel type. Previously, we documented in mice myeloid cell association with the brain vasculature but did not distinguish their localization along the vascular tree. Using molecular approaches to distinguish microglia and perivascular macrophages, we show that microglia are the only myeloid cells associating with capillaries. To determine if loss of microglia is sufficient to reduce capillary tone, we employ global and focal ablations and find significant reductions in capillary diameter and red blood cell flux, suggesting vasodilatory regulation by microglia. Cyclooxygenase-1 (COX1), an enzyme with known vasodilatory action, is predominantly expressed by microglia. To determine the necessity of microglial COX1 in regulating cerebral basal capillary tone in vivo, we perform genetic ablation and find a significant reduction in capillary flux and diameter. Together, this study using male mouse models reveals a role for microglial COX1 in maintaining basal capillary tone in vivo.
小胶质细胞和边界相关巨噬细胞与高碳酸血症有关，但尚不清楚哪种髓样细胞调节哪种血管类型。此前，我们记录了小鼠中髓样细胞与脑血管系统的关联，但未区分它们沿血管树的定位。使用分子方法区分小胶质细胞和血管周围巨噬细胞，我们发现小胶质细胞是唯一与毛细血管相关的髓样细胞。为了确定小胶质细胞的缺失是否足以降低毛细血管张力，我们采用了整体和局部消融方法，发现毛细血管直径和红细胞通量显著降低，提示小胶质细胞具有血管舒张调节作用。环氧化酶-1（COX1）是一种具有已知血管舒张作用的酶，主要由小胶质细胞表达。为了确定小胶质细胞COX1在体内调节脑基底毛细血管张力中的必要性，我们进行了基因消融，发现毛细血管通量和直径显著降低。总之，这项使用雄性小鼠模型的研究揭示了小胶质细胞COX1在体内维持基底毛细血管张力中的作用。
