Abstract 061: Loss of Lymphocyte Adaptor Protein LNK Promotes Acute Aortic Dissection
In: Hypertension, Jg. 70 (2017-09-01)
Online
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Zugriff:
Background: Acute aortic dissection (AD) is a life-threatening vascular disease associated with an inflammatory response. A polymorphism in the gene SH2B3 that encodes LNK has been associated with several cardiovascular and autoimmune diseases in humans. LNK is an adaptor protein expressed in hematopoietic and endothelial cells that serves as a brake to cellular proliferation and cytokine production. We hypothesize that loss of LNK promotes AD through an exacerbation of the acute immune response. Methods: Angiotensin II (Ang II) was infused for 3 or 14 days into wild type (WT) and LNK -/- mice. Kaplan-Meier survival curves were generated. After 3 days, the aortic remodeling was accessed by standard histological staining methods and microscopy. The aortic inflammation was characterized by flow cytometry and immunohistochemistry. Results: Ang II infusion induces a rapid and drastic mortality in LNK -/- mice compared to WT mice (66% vs 8%, P -/- mice show significant remodeling with more elastin fragmentation than WT mice (10.5 vs 4.6 breaks, P 4 μm 2 , P =0.057). Strikingly, collagen qualitative analysis reveals thinner collagen fibers and several areas of disruption and disorganization in the aorta of LNK -/- mice prior to AD development. In parallel, the aorta of LNK -/- mice show an increase in the number of neutrophils and macrophages but not in T cells compared to WT mice. Conclusion: In our model, LNK seems to play a key role in maintaining the aortic wall integrity. Loss of LNK promotes acute inflammation and matrix degradation, leading to the development of AD. Targeting LNK could be a potential therapeutic strategy for the management of aortic dissection.
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Abstract 061: Loss of Lymphocyte Adaptor Protein LNK Promotes Acute Aortic Dissection
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Autor/in / Beteiligte Person: | Madhur, Meena S. ; Gavulic, Kyle A. ; Laroumanie, Fanny ; Saleh, Mohamed A. ; McMaster, William G. ; Dale, Bethany L. |
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Zeitschrift: | Hypertension, Jg. 70 (2017-09-01) |
Veröffentlichung: | Ovid Technologies (Wolters Kluwer Health), 2017 |
Medientyp: | unknown |
ISSN: | 1524-4563 (print) ; 0194-911X (print) |
DOI: | 10.1161/hyp.70.suppl_1.061 |
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