Abstract 153: NKT Cells Aggravate the Development of Abdominal Aortic Aneurysms

Abstract

Background: An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta mainly affecting men aged 60 years or older. Development of AAA is associated with an accumulation of inflammatory cells in the lesions such as NKT cells. The goal of this study was to investigate the exact contribution of these cells in angiotensin II (AngII) induced AAA formation in LDLr -/- mice. Methods & Results: To investigate the role of NKT cells in AAA formation, LDLr -/- and LDLr -/- CD1d -/- (NKT cell deficient) mice were fed a Western type diet for one week prior to infusion with AngII using osmotic minipumps. During the experiment, 5 out of 12 LDLr -/- mice died due to a rupture of the aorta while 0 out of 11 LDLr -/- CD1d -/- mice died. Four weeks after placement of minipumps, the mice were sacrificed and a clear significant difference in AAA-severity was observed. In 7 out of 11 LDLr -/- CD1d -/- mice no AAA lesions were found compared with only 1 out of 12 LDLr -/- mice. Furthermore, ex vivo studies show that glycolipid-induced NKT cell activation upregulates the expression of MMP-12, cathepsin-S and -L on macrophages and MMP-12, cathepsin-S and -K on vascular smooth muscle cells (vSMCs) and in addition a reduction in vSMC viability is induced after activation of NKT cells. Conclusions: These data show that NKT cells aggravate the development of AngII-induced AAA by inducing degeneration of the extracellular matrix of the vessel wall. These results provide new opportunities to intervene in the development of aneurysms.