Indomethacin Prevents the Progression of Thoracic Aortic Aneurysm in Marfan Syndrome Mice

Aorta : Official Journal of the Aortic Institute at Yale-New Haven Hospital
Gao GuoPeter N Robinson

Abstract

Marfan syndrome (MFS), an inherited disorder of connective tissue characterized by abnormalities in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The high mortality in untreated patients is primarily due to aneurysm and dissection of the ascending aorta. The complex pathogenesis of MFS involves changes in transforming growth factor β (TGF-β) signaling, increased matrix metalloproteinase (MMP) expression, and fragmentation of the extracellular matrix. A number of studies have demonstrated increased counts of macrophages and T cells in the ascending aorta of persons or mouse models of MFS, but the efficacy of anti-inflammatory therapy in mouse models of MFS has not yet been assessed. FBN1 underexpressing mgR/mgR Marfan mice were treated with oral indomethacin. Treatment was begun at the age of three weeks and continued for 8 weeks, following which the aorta of wild type as well as treated and untreated mgR/mgR mice was compared. Indomethacin treatment led to a statistically significant reduction of aortic elastin degeneration and macrophage infiltration, as well as a lessening of MMP-2, MMP-9, and MMP-12 upregulation. Additionally, indomethacin decreased both cyclooxy...Continue Reading

Citations

Jan 18, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Dianna M Milewicz, Francesco Ramirez
Jan 25, 2019·Journal of Cellular and Molecular Medicine·Raghu BhushanPeter N Robinson
Nov 3, 2017·Health Economics·Christopher J CroninIlene S Speizer
Jun 13, 2021·Experimental Cell Research·Xipeng WangXiaoming Zhang
May 1, 2019·Cerebrovascular Diseases Extra·Courtney L Fisher, Stacie L Demel

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