Abstract 220: Deficiency in Triggering Receptor Expressed in Myeloid Cells-1 Substantially Attenuates Atherosclerotic Lesion Development
TREM-1 is a potent amplifier of pro-inflammatory responses in myeloid cells. While the significance of TREM-1 in acute microbial-induced septic shock has long been acknowledged, our previous studies in experimental models of colitis have also suggested an important role for TREM-1 in driving non-infectious and chronic inflammatory diseases.
Here, we aim to define the role of TREM-1 in atherosclerosis, which is recognized as a chronic inflammatory disorder of the arteries with a major involvement of monocytes and macrophages. TREM-1-deficient (Trem1-/-) mice were backcrossed with apolipoprotein E-deficient (Apoe-/-) mice and were fed a high cholesterol/fat diet for 16 weeks. Compared with Trem1+/+ Apoe-/- mice, Trem1-/- Apoe-/- mice were substantially protected from diet-induced atherosclerosis. Interestingly, while the number of individual atherosclerotic plaques did not differ between the two groups of mice, the average lesion size and total surface area of atherosclerotic lesions were significantly reduced in Trem1-/- Apoe-/- mice. Moreover, analysis of early atherosclerotic lesions revealed no difference between the two groups. Hence, TREM-1 appears to be involved in the progression, rather than the initiation of atherosclerotic lesions. In line with the reduced lesion size, FACS analysis of aortic cell preparations revealed substantially lower frequencies of infiltrating CD11b+ myeloid cells in Trem1-/- Apoe-/- mice. To gain insight into the underlying mechanisms of TREM-1-mediated effects in atherogenesis, we are currently analyzing mRNA expression profiles of aortic segments derived from Trem1+/+ Apoe-/- and Trem1-/- Apoe-/- mice. These studies will be complemented by immunohistochemistry stainings and by in vitro studies that are aimed to directly determine the impact of TREM-1 on foam cell generation and cholesterol efflux.
Author Disclosures: D. Zysset: None. B. Weber: None. S. Rihs: None. S. Freigang: None. Y. Banz: None. L. Saurer: None. C. Mueller: None.
- © 2015 by American Heart Association, Inc.