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Abstract Number: 0042

The Pathogenic Role of Lymphatic Vessels in Autoimmune Valvular Carditis

Amritha Yellamilli1, Victoria Osinski2, Maria Firulyova3, Jennifer Auger4, Lee Meier2, Jessica Faragher5, Aubyn Marath6, Konstantin Zaitsev3 and Bryce Binstadt5, 1Stanford University School of Medicine, Palo Alto, 2University of Minnesota School of Medicine, Minneapolis, MN, 3ITMO University, Saint Petersburg, Russia, 4University of Minnesota Medical School, Minneapolis, MN, 5University of Minnesota, Minneapolis, MN, 6CardioStart, Portland

Meeting: ACR Convergence 2022

Keywords: Angiogenesis, Animal Model, autoimmune diseases, Cardiovascular, Pediatric rheumatology

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Session Information

Date: Saturday, November 12, 2022

Title: Pediatric Rheumatology – Basic Science Poster

Session Type: Poster Session A

Session Time: 1:00PM-3:00PM

Background/Purpose: Valvular carditis is a serious complication of systemic autoimmune diseases. Although endothelial cells are thought to play an important role in autoimmune valvular carditis, little is known about their specific roles in this disease process.

Methods: We performed in vivo lineage tracing of endothelial cells in the K/B.g7 mouse model of systemic autoimmune arthritis and valvular carditis. Using immunofluorescent staining and imaging, we characterized and quantified endothelial cells during the progression of autoimmune valvular carditis in K/B.g7 mice. We then used single-cell RNA sequencing to further characterize lymphatic endothelial cells isolated from inflamed K/B.g7 valves using unsupervised cluster analysis and differential gene expression. Finally, we performed immunofluorescent staining and imaging of mitral valves from patients with rheumatic heart disease.

Results: We identified lymphatic endothelial cell networks within inflamed mitral valves of K/B.g7 mice. We showed that these networks expand and acquire a pro-fibrotic phenotype during the progression of autoimmune valvular carditis. Blocking lymphangiogenesis using a small molecular inhibitor of VEGFR-3 reduced inflammation and fibrosis of mitral valves in K/B.g7 mice but did not affect the development of arthritis. Importantly, we identified VEGFR-3-expressing lymphatic vessels in mitral valves of patients with rheumatic heart disease.

Conclusion: Our study shows that lymphangiogenesis is a maladaptive, pro-fibrotic process that can be therapeutically targeted in patients with autoimmune valvular carditis.


Disclosures: A. Yellamilli, None; V. Osinski, None; M. Firulyova, None; J. Auger, None; L. Meier, None; J. Faragher, None; A. Marath, None; K. Zaitsev, None; B. Binstadt, Pfizer, Pfizer.

To cite this abstract in AMA style:

Yellamilli A, Osinski V, Firulyova M, Auger J, Meier L, Faragher J, Marath A, Zaitsev K, Binstadt B. The Pathogenic Role of Lymphatic Vessels in Autoimmune Valvular Carditis [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/the-pathogenic-role-of-lymphatic-vessels-in-autoimmune-valvular-carditis/. Accessed .
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All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

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