Document Type
Article
Publication Date
5-2026
Abstract
Introduction: Inflammatory bowel disease involves aberrant immune responses and is associated with both cardiovascular disease risk and altered intestinal blood flow. However, little is known about how inflammatory bowel disease affects regulation of perivascular nerves that mediate blood flow. Previous work found perivascular nerve function is impaired in mesenteric arteries with Inflammatory bowel disease. The purpose of this study was to determine the mechanism of impaired perivascular nerve function.
Methods: RNA sequencing was performed on mesenteric arteries from IL10−/− mice treated with H. hepaticus to induce disease (inflammatory bowel disease) or left non-gavaged (Control). For all other studies, Control and Inflammatory bowel disease mice received either saline or clodronate liposome injections to study the effect of macrophage depletion. Perivascular nerve function was assessed using pressure myography and electrical field stimulation. Leukocyte populations, and perivascular nerves, and adventitial neurotransmitter receptors were labeled using fluorescent immunolabeling.
Results: Inflammatory bowel disease was associated with increases in macrophage-associated gene expression, and immunolabeling showed accumulation of adventitial macrophages. Clodronate liposome injection eliminated adventitial macrophages, which reversed significant attenuation of sensory vasodilation, sympathetic vasoconstriction and sensory inhibition of sympathetic constriction in inflammatory bowel disease. Acetylcholinemediated dilation was impaired in inflammatory bowel disease and restored after macrophage depletion, but sensory dilation remained nitric oxide independent regardless of disease and/or macrophage presence.
Conclusion: Altered neuro-immune signaling between macrophages and perivascular nerves in the arterial adventitia contributes to impaired vasodilation, particularly via dilatory sensory nerves. Targeting the adventitial macrophage population may help preserve intestinal blood flow in Inflammatory bowel disease patients.
Recommended Citation
Grunz EA, Jones BW, Lateef OM, Sen S, Wilkinson K, Joshi T and Boerman EM (2023), Adventitial macrophage accumulation impairs perivascular nerve function in mesenteric arteries with inflammatory bowel disease. Front. Physiol. 14:1198066. doi: 10.3389/fphys.2023.1198066
Included in
Cardiovascular Diseases Commons, Digestive System Diseases Commons, Molecular and Cellular Neuroscience Commons
Comments
The copy of record is available from the publisher at https://doi.org/10.3389/fphys.2023.1198066. © 2023 Grunz, Jones, Lateef, Sen, Wilkinson, Joshi and Boerman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).