Abstract
Abstract Tu0036: Habitual Exercise Modulates Neuro-Immune Interaction to Mitigate Aortic Stiffness
Arteriosclerosis, thrombosis, and vascular biology, Vol.45(Suppl_1), pp.ATu0036-ATu0036
04/2025
DOI: 10.1161/atv.45.suppl_1.Tu0036
Abstract
Background: Exercise augments hemodynamic shear to activate mechano-sensitive molecular transducers in the vascular endothelium. Recently, we and others observed that the central nervous system mediates neuro-immune interaction in the aortic adventitia (AA). Whether exercise modulates the sympathetic nerve interaction with the immune cells to mitigate aortic stiffness remains unknown.
Methods and Results: Four weeks of Angiotensin II (Ang II) infusion to C57BL/6 mice increased neural activation to increase the expression of tyrosine hydroxylase (TH) for sympathetic nerve axons and norepinephrine levels along with the colocalization of synapsin and β2-adrenergic receptor positive macrophages in the AA. This Ang II-mediated sympathetic nerve and macrophage interaction activated fibroblasts to increase vascular fibrotic remodeling, aortic pulse wave velocity (PWV), and blood pressure. Sympathetic denervation with celiac ganglionectomy or 6-hydroxydopamine treatment abrogated Ang II-mediated TH+, reducing AA thickness and PWV. scRNAseq analyses of the AA revealed that Ang II increased the circulating monocyte-derived macrophages (Ccr2+CD80+) but reduced the resident macrophages (Lyve1+CD163+). Gene ontology analysis of differentially expressed genes unveiled that voluntary wheel running (VWR) mitigated Ang II-mediated increase in Ccr2+CD80 macrophages, cytokines-mediated signaling pathways in macrophages, and ECM deposition in fibroblasts. Macrophage depletion with Ki20227 (colony stimulating factor-1 receptor inhibitor) reduced Ang II-mediated synapsin+ macrophages. Using the Ccr2 knock-in (Ccr2gfp) / knock-out (Ccr2KO) mice, we observed that Ang II-mediated increases in Ccr2+ macrophages were expressed in Ccr2GFP mice but were absent in Ccr2KO mice. Also, Ang II-induced increases in synapsin expression, neighboring Ccr2+ cells, AA thickness, and PWV were reduced in Ccr2KOmice. Both Ki20227 (colony-stimulating factor 1 receptor inhibitor) and Ccr2KO significantly reduced the Ang II-mediated increase in TH levels. scRNAseq results also revealed that four weeks of VWR further abrogated Ang II-mediated macrophage-to-fibroblast communication via IL-1β signaling in AA, and this communication was supported by using human macrophage and aortic adventitia fibroblast cell lines.
Conclusions: Exercise mitigates Ang II-mediated sympathetic nerve axons interaction with the macrophages in the AA to ameliorate vascular fibrotic remodeling and aortic stiffness.
Details
- Title: Subtitle
- Abstract Tu0036: Habitual Exercise Modulates Neuro-Immune Interaction to Mitigate Aortic Stiffness
- Creators
- Jae Min Cho - UCLA SCH OF MED CARDIOLOGY DIV, Los Aeles, California, United StatesKhoa Vu - University of California Los Angele, Westminster, California, United StatesEnbo Zhu - UCLA SCH OF MED CARDIOLOGY DIV, Los Aeles, California, United StatesSeul Ki Park - UCLA SCH OF MED CARDIOLOGY DIV, Los Aeles, California, United StatesCharlie Li - University of California Los Angele, Westminster, California, United StatesPeng Zhao - UCLA SCH OF MED CARDIOLOGY DIV, Los Aeles, California, United StatesLilly Yang - University of California Los Angele, Westminster, California, United StatesRong Lu - LAC+USC Medical CenterYang Xiang - University of California, DavisMark Chapleau - University of IowaYing Shen - Baylor College of MedicineTzung Hsiai - UCLA SCH OF MED CARDIOLOGY DIV, Los Aeles, California, United States
- Resource Type
- Abstract
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.45(Suppl_1), pp.ATu0036-ATu0036
- DOI
- 10.1161/atv.45.suppl_1.Tu0036
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Publisher
- Lippincott Williams & Wilkins
- Language
- English
- Date published
- 04/2025
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984832081902771
Metrics
2 Record Views