TREM-1 orchestrates angiotensin II-induced monocyte trafficking and promotes experimental abdominal aortic aneurysm.

  • Platform National Cytometry
January 19, 2021 By:
  • Vandestienne M
  • Zhang Y
  • Santos-Zas I
  • Al-Rifai R
  • Joffre J
  • Giraud A
  • Laurans L
  • Esposito B
  • Pinet F
  • Bruneval P
  • Raffort J
  • Lareyre F
  • Vilar J
  • Boufenzer A
  • Guyonnet L
  • Guerin C
  • Clauser E
  • Silvestre JS
  • Lang S
  • Soulat-Dufour L
  • Tedgui A
  • Mallat Z
  • Taleb S
  • Boissonnas A
  • Derive M
  • Chinetti G
  • Ait-Oufella H.

The triggering receptor expressed on myeloid cells 1 (TREM-1) drives inflammatory responses in several cardiovascular diseases but its role in abdominal aortic aneurysm (AAA) remains unknown. Our objective was to explore the role of TREM-1 in a mouse model of angiotensin II-induced (AngII-induced) AAA. TREM-1 expression was detected in mouse aortic aneurysm and colocalized with macrophages. Trem1 gene deletion (Apoe-/-Trem1-/-), as well as TREM-1 pharmacological blockade with LR-12 peptide, limited both AAA development and severity. Trem1 gene deletion attenuated the inflammatory response in the aorta, with a reduction of Il1b, Tnfa, Mmp2, and Mmp9 mRNA expression, and led to a decreased macrophage content due to a reduction of Ly6Chi classical monocyte trafficking. Conversely, antibody-mediated TREM-1 stimulation exacerbated Ly6Chi monocyte aorta infiltration after AngII infusion through CD62L upregulation and promoted proinflammatory signature in the aorta, resulting in worsening AAA severity. AngII infusion stimulated TREM-1 expression and activation on Ly6Chi monocytes through AngII receptor type I (AT1R). In human AAA, TREM-1 was detected and TREM1 mRNA expression correlated with SELL mRNA expression. Finally, circulating levels of sTREM-1 were increased in patients with AAA when compared with patients without AAA. In conclusion, TREM-1 is involved in AAA pathophysiology and may represent a promising therapeutic target in humans.

2021 Jan. J Clin Invest.131(2).
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