TREM-1 orchestrates angiotensin II–induced monocyte trafficking and promotes experimental abdominal aortic aneurysm
Marie Vandestienne
(1)
,
Yujiao Zhang
(1)
,
Icia Santos-Zas
(1)
,
Rida Al-Rifai
(1)
,
Jeremie Joffre
(2)
,
Andreas Giraud
(1)
,
Ludivine Laurans
(1)
,
Bruno Esposito
(1)
,
Florence Pinet
(3)
,
Patrick Bruneval
(1, 4)
,
Juliette Raffort
(5, 6)
,
Fabien Lareyre
(5, 6)
,
Jose Vilar
(1)
,
Amir Boufenzer
(7)
,
Lea Guyonnet
(8, 9, 10)
,
Coralie Guerin
(8, 9, 10)
,
Eric Clauser
(1)
,
Jean-Sébastien Silvestre
(1)
,
Sylvie Lang
(11, 12)
,
Laurie Soulat-Dufour
(11, 12)
,
Alain Tedgui
(1)
,
Ziad Mallat
(1, 13)
,
Soraya Taleb
(1)
,
Alexandre Boissonnas
(14)
,
Marc Derive
(7)
,
Giulia Chinetti
(5, 6)
,
Hafid Ait-Oufella
(1, 11)
1
PARCC (UMR_S 970/ U970) -
Paris-Centre de Recherche Cardiovasculaire
2 UC San Francisco - University of California [San Francisco]
3 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 CHU Nice - Centre Hospitalier Universitaire de Nice
6 C3M - Centre méditerranéen de médecine moléculaire
7 INOTREM SA
8 Institut Curie [Paris]
9 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
10 LIH - Luxembourg Institute of Health
11 CHU Saint-Antoine [AP-HP]
12 SU - Sorbonne Université
13 CAM - University of Cambridge [UK]
14 CIMI - Centre d'Immunologie et des Maladies Infectieuses
2 UC San Francisco - University of California [San Francisco]
3 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 CHU Nice - Centre Hospitalier Universitaire de Nice
6 C3M - Centre méditerranéen de médecine moléculaire
7 INOTREM SA
8 Institut Curie [Paris]
9 IThEM - U1140 - Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis
10 LIH - Luxembourg Institute of Health
11 CHU Saint-Antoine [AP-HP]
12 SU - Sorbonne Université
13 CAM - University of Cambridge [UK]
14 CIMI - Centre d'Immunologie et des Maladies Infectieuses
Marie Vandestienne
- Fonction : Auteur
- PersonId : 1179986
- ORCID : 0000-0002-6947-9852
Yujiao Zhang
- Fonction : Auteur
- PersonId : 1179987
- ORCID : 0000-0002-0982-858X
Rida Al-Rifai
- Fonction : Auteur
- PersonId : 175150
- IdHAL : rida-al-rifai
- ORCID : 0000-0002-6976-0011
Florence Pinet
- Fonction : Auteur
- PersonId : 9887
- IdHAL : florence-pinet
- ORCID : 0000-0002-5471-1487
- IdRef : 033124701
Patrick Bruneval
- Fonction : Auteur
- PersonId : 756352
- ORCID : 0000-0002-2350-2914
Fabien Lareyre
- Fonction : Auteur
- PersonId : 779175
- ORCID : 0000-0002-6765-8021
Eric Clauser
- Fonction : Auteur
- PersonId : 1177175
- ORCID : 0000-0003-1535-869X
Jean-Sébastien Silvestre
- Fonction : Auteur
- PersonId : 1079451
- ORCID : 0000-0003-3962-2205
- IdRef : 112239889
Alain Tedgui
- Fonction : Auteur
- PersonId : 1167567
- ORCID : 0000-0002-7229-4875
Ziad Mallat
- Fonction : Auteur
- PersonId : 1179988
- ORCID : 0000-0003-0443-7878
Soraya Taleb
- Fonction : Auteur
- PersonId : 1179989
- ORCID : 0000-0002-6650-619X
Résumé
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.