Details

Autor(en) / Beteiligte

• Hendrikx, Tim
• Jeurissen, Mike L. J
• Gorp, Patrick J
• Gijbels, Marion J
• Walenbergh, Sofie M. A
• Houben, Tom
• Gorp, Rick
• Pöttgens, Chantal C
• Stienstra, Rinke
• Netea, Mihai G
• Hofker, Marten H
• Donners, Marjo M. P. C
• Shiri‐Sverdlov, Ronit

Titel

Bone marrow‐specific caspase‐1/11 deficiency inhibits atherosclerosis development in Ldlr−/− mice

Ist Teil von

• The FEBS journal, 2015-06, Vol.282 (12), p.2327-2338

Ort / Verlag

England: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Ly6Cʰⁱᵍʰ monocytes and an increased level of Ly6Cˡᵒʷ 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.