Journal article
Wei Chen, Justin P. Van Beusecum, Liang Xiao, David M. Patrick, Mingfang Ao, Shilin Zhao, C. Cavinato, Alexander W. Caulk, Jay D. Humphrey, David G. Harrison
HYPERTENSION, 2022
HYPERTENSION, 2022
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APA
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Chen, W., Beusecum, J. P. V., Xiao, L., Patrick, D. M., Ao, M., Zhao, S., … Harrison, D. G. (2022). Abstract P236: Role Of Axl In Target Organ Inflammation And Damage Due To Hypertensive Aortic Remodeling. HYPERTENSION.
Chicago/Turabian
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Chen, Wei, Justin P. Van Beusecum, Liang Xiao, David M. Patrick, Mingfang Ao, Shilin Zhao, C. Cavinato, Alexander W. Caulk, Jay D. Humphrey, and David G. Harrison. “Abstract P236: Role Of Axl In Target Organ Inflammation And Damage Due To Hypertensive Aortic Remodeling.” HYPERTENSION (2022).
MLA
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Chen, Wei, et al. “Abstract P236: Role Of Axl In Target Organ Inflammation And Damage Due To Hypertensive Aortic Remodeling.” HYPERTENSION, 2022.
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@article{wei2022a,
title = {Abstract P236: Role Of Axl In Target Organ Inflammation And Damage Due To Hypertensive Aortic Remodeling},
year = {2022},
journal = {HYPERTENSION},
author = {Chen, Wei and Beusecum, Justin P. Van and Xiao, Liang and Patrick, David M. and Ao, Mingfang and Zhao, Shilin and Cavinato, C. and Caulk, Alexander W. and Humphrey, Jay D. and Harrison, David G.}
}
Abstract
Background: Aortic remodeling enhances arterial pulsatility in the microcirculation and we have shown that excessive endothelial stretch increases release of Growth Arrest Specific 6 (GAS6), which activates Axl on monocytes causing immune activation and inflammation.
Hypothesis: GAS6/Axl blockade reduces renal and vascular inflammation and lessens renal dysfunction caused by aortic remodeling.
Methods and Results: Three month old male C57Bl/6 mice received osmotic minipumps containing vehicle or ang II for 2 weeks and the pumps removed. Aortas demonstrated increased collagen and an 80% loss of Windkessel function that persisted for 6 months following ang II. Renal function studies showed reduced ability to excrete a volume load, a progressive increase in albuminuria and tubular damage as estimated by Periodic Acid Schiff staining. Treatment with the Axl inhibitor R428 beginning 2 months after ang II had minimal effect on aortic remodeling 2 months later, but reduced aortic and renal infiltration of T cells, gamma/delta T cells and macrophages as measured by flow cytometry (Figure). R428 also improved renal excretory capacity, decreased urinary NGAL, reduced albuminuria, and attenuated renal tubular damage. Interestingly, macrophage/T cell complexes were present in aortas of mice previously exposed to hypertension, and were reduced by R428.
Conclusion: Brief episodes of hypertension induce chronic aortic remodeling which increases Axl signaling and transformation of monocytes to inflammatory antigen presenting cells that activate T cells. Axl blockade might serve as a therapeutic option to improve end-organ damage after an episode of hypertension.