In:
The FEBS Journal, Wiley, Vol. 282, No. 12 ( 2015-06), p. 2327-2338
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 1β ( IL ‐1β) 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.
Type of Medium:
Online Resource
ISSN:
1742-464X
,
1742-4658
DOI:
10.1111/febs.2015.282.issue-12
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2172518-4
SSG:
12
Bookmarklink