Bone marrow-specific caspase-1/11 deficiency inhibits atherosclerosis development in Ldlr(-/-) mice.
FEBS J
; 282(12): 2327-38, 2015 Jun.
Article
in En
| MEDLINE
| ID: mdl-25817537
ABSTRACT
Recent investigations have suggested that inflammasome activation plays an important role during atherosclerosis. Upon activation, the inflammasome induces processing and release of pro-inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 18 (IL-18) via activation of caspase-1/11. Previously, it was shown that complete caspase-1 deficiency is protective against atherosclerosis development. However, while macrophages are the main inflammatory cells involved in atherosclerosis, the exact role of macrophage-specific caspase-1/11 activation during development of cardiovascular disease has never been investigated. We hypothesized that hematopoietic caspase-1/11 deficiency leads to reduced atherosclerosis development. To investigate the specific contribution of hematopoietic caspase-1/11 activation to atherosclerosis development, Ldlr(-/-) mice received a transplant (tp) of wild-type (WT) or caspase-1/11(-/-) bone marrow, to create WT-tp mice and caspase-1/11(-/-) -tp mice, and fed a high-fat, high-cholesterol diet for 12 weeks. Our results showed an increase in anti-inflammatory blood leukocytes in caspase-1/11(-/-) -tp mice compared with WT-tp mice, as indicated by a decreased level of Ly6C(high) monocytes and an increased level of Ly6C(low) monocytes. In line with our hypothesis, hematopoietic deletion of caspase-1/11 resulted in a strong reduction in atherosclerotic plaque size. Furthermore, necrotic core content was dramatically decreased in caspase-1/11(-/-) -tp mice. Our data indicate that hematopoietic caspase-1/11 activation is involved in vascular inflammation and atherosclerosis, and plays an important role in cardiovascular disease progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aorta, Thoracic
/
Receptors, LDL
/
Monocytes
/
Caspases
/
Caspase 1
/
Atherosclerosis
/
Leukocytes
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
FEBS J
Journal subject:
BIOQUIMICA
Year:
2015
Document type:
Article
Affiliation country:
Netherlands