CD1d deficiency inhibits the development of abdominal aortic aneurysms in LDL receptor deficient mice

Gijs H.M. Van Puijvelde*, Amanda C. Foks, Rosemarie E. van Bochove, Ilze Bot, Kim L.L. Habets, Saskia C. De Jager, Mariëtte N.D. ter Borg, Puck van Osch, Louis Boon, Mariska Vos, Vivian De Waard, Johan Kuiper

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta leading to serious complications and mostly to death. AAA development is associated with an accumulation of inflammatory cells in the aorta including NKT cells. An important factor in promoting the recruitment of these inflammatory cells into tissues and thereby contributing to the development of AAA is angiotensin II (Ang II). We demonstrate that a deficiency in CD1d dependent NKT cells under hyperlipidemic conditions (LDLr-/-CD1d-/- mice) results in a strong decline in the severity of angiotensin II induced aneurysm formation when compared with LDLr-/- mice. In addition, we show that Ang II amplifies the activation of NKT cells both in vivo and in vitro. We also provide evidence that type I NKT cells contribute to AAA development by inducing the expression of matrix degrading enzymes in vSMCs and macrophages, and by cytokine dependently decreasing vSMC viability. Altogether, these data prove that CD1d-dependent NKT cells contribute to AAA development in the Ang II-mediated aneurysm model by enhancing aortic degradation, establishing that therapeutic applications which target NKT cells can be a successful way to prevent AAA development.

Original languageEnglish
Article numbere0190962
JournalPLoS ONE
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018
Externally publishedYes

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