Single-cell RNA sequencing identifies interferon-inducible monocytes/macrophages as a cellular target for mitigating the progression of abdominal aortic aneurysm and rupture risk.
Cardiovasc Res
; 120(11): 1351-1364, 2024 Sep 21.
Article
en En
| MEDLINE
| ID: mdl-38836630
ABSTRACT
AIMS:
Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signalling pathways involved in the development and progression of AAAs is essential for the development of medical therapy. METHODS ANDRESULTS:
We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, and identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the AAAs. Gene set variation analysis revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/-; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate, and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signalling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs.CONCLUSION:
IFNICs are a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aorta Abdominal
/
Rotura de la Aorta
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Angiotensina II
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Monocitos
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Transducción de Señal
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Aneurisma de la Aorta Abdominal
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Progresión de la Enfermedad
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Modelos Animales de Enfermedad
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Receptor de Interferón alfa y beta
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Análisis de la Célula Individual
Idioma:
En
Revista:
Cardiovasc Res
Año:
2024
Tipo del documento:
Article
País de afiliación:
China