CD40L Deficiency Protects Against Aneurysm Formation

• DOI: 10.1161/atvbaha.117.310640
• Publication Date: 2018-03-09T10:47:10Z
• Authors: Pascal J.H. Kusters; Tom T.P. Seijkens; Linda Beckers; Dirk Lievens; Holger Winkels; Vivian de Waard; Adriaan Duijvestijn; Moritz Lindquist ...; Joy Roy; Alan Daugherty; Andrew Newby; Norbert Gerdes; Esther Lutgens
• Keywords: Apolipoprotein E; Proinflammatory cytokine

The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration aortic wall, we studied role costimulatory molecule CD40L, major driver inflammation, in aneurysm formation.Transcriptomics data obtained from human abdominal and normal aortas revealed increased abundance both CD40L CD40 media thrombus-free thrombus-covered samples. To further unravel formation, apolipoprotein E-deficient (Apoe-/-) Cd40l-/-Apoe-/- mice were infused with angiotensin II for 7 28 days. Only minority (33% 17%) developed (dissecting) compared 75% 67% Apoe-/- littermates after days infusion, respectively. Total vessel area aorta at suprarenal level was 52% smaller II-infused that mice. Chimeric repopulated bone marrow afforded similar protection against dissecting formation. Moreover, lack protected fatal rupture. T helper cell macrophage accumulation aneurysmal tissue reduced concomitant decrease expression proinflammatory chemo- cytokines. In addition, displayed matrix metalloproteinase-13 an increase inhibitor metalloproteinase-3 while activity metalloproteinase-2 metalloproteinase-9 diminished.Deficiency (hematopoietic) protects reduces incidence This associated decreased activation inflammatory cells dampened protease wall.