Abstract
Abstract 16975: Wheel-Running Exercise Abrogates Enhanced Sympathetic Neural-Immune Interface in Aortic Adventitia of Angiotensin II-Infused Hypertensive Mice
Circulation (New York, N.Y.), Vol.148(Suppl_1)
11/07/2023
DOI: 10.1161/circ.148.suppl_1.16975
Abstract
Abstract only Background: Artery stiffness causes cardiovascular pathology. Although mechanisms underlying endothelial dysfunction and arterial stiffness are well characterized, it is unknown if neural-immune interaction in aortic adventitia (AA) influences arterial stiffness. We hypothesized that sympathetic innervation and CD68 + macrophages are increased in AA of Angiotensin II (Ang II)-infused mice leading to increased arterial fibrosis and stiffness, and that voluntary wheel-running exercise (VWR) mitigates these effects. Methods and Results: In eight-week-old C57BL/6 male mice, Ang II was infused at 1.5 μg/g/day for 4 weeks with and without VWR. Mean arterial blood pressure [MAP] measured by tail-cuff averaged 135±11 mmHg in Ang II-infused mice (n=5) and 90±10 mmHg in vehicle-infused mice (n=4). Staining for markers of nerve fibers/bundles with Neurofilament A (NF200), sympathetic nerves with tyrosine hydroxylase (TH), nerve endings in AA with synapsin, and CD68 + macrophages were all increased in AA removed from Ang II-infused mice compared with vehicle-infused mice. The increases in CD68 + macrophages and extracellular matrix (ECM) were associated with elevated pulse wave velocity (PWV), an index for arterial stiffness (Ang II: p < 0.05 vs. vehicle). scRNA-seq analyses further corroborated that Ang II infusion promoted fibrosis and macrophage-associated genes in AA. VWR significantly attenuated the Ang II-induced increases in MAP, sympathetic innervation, CD68 + expression, ECM, and PWV (Ang II+VWR: all p<0.05 vs. Ang II). To chemically “denervate” the sympathetic nervous system, we injected 6-hydroxydopamine (6-OHDA, 100 mg/kg on day 0 and 250 mg/kg on day 2, then weekly for 4 weeks) or vehicle in Ang II-infused mice. 6-OHDA decreased MAP, sympathetic innervation, macrophage expression, ECM accumulation, and PWV (Ang II+6-OHDA: p<0.05 vs. Ang II+vehicle, n=3). Conclusion: Ang II-induced hypertensive mice develop increases in sympathetic innervation and macrophages in close proximity within AA that define an enhanced sympathetic neural-immune interface in association with vascular fibrosis, arterial stiffness, and hypertension. VWR significantly mitigates these pathophysiological responses.
Details
- Title: Subtitle
- Abstract 16975: Wheel-Running Exercise Abrogates Enhanced Sympathetic Neural-Immune Interface in Aortic Adventitia of Angiotensin II-Infused Hypertensive Mice
- Creators
- Jae Min Cho - University of California, Los AngelesEnbo Zhu - University of California, Los AngelesMehrdad Roustaei - BioengineeringKhoa Vu - University of California, Los AngelesJonah Nahoul - University of California, Los AngelesMark W Chapleau - University of IowaTzung K Hsiai - University of California, Los Angeles
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.148(Suppl_1)
- DOI
- 10.1161/circ.148.suppl_1.16975
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/07/2023
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984539442302771
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