Related Experiment Video
Updated: May 5, 2026
Mouse Models for Graft Arteriosclerosis
Published on: May 14, 2013
Atherosclerosis Deteriorates Liver Ischemia/Reperfusion Injury Via Interferon Regulatory Factor-1 Overexpression in a
Ryosuke Nakano1, Ichiya Chogahara1, Masahiro Ohira2
1Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
Insights
Atherosclerosis exacerbates liver injury following ischemia/reperfusion by activating immune cells. This study reveals atherosclerosis mirrors intrahepatic immunity, increasing liver damage via IL-15 and IRF-1 pathways.
Area of Science:
- Immunology
- Hepatology
- Cardiovascular Research
Background:
- Abdominal aortic calcification (AAC) links to cardiovascular mortality and poor outcomes post-hepatectomy for hepatocellular carcinoma.
- The impact of atherosclerosis on systemic inflammation and response to ischemia/reperfusion injury (IRI) is not well understood.
Purpose of the Study:
- To investigate how atherosclerosis affects the liver immune system during warm ischemia/reperfusion injury (IRI).
Main Methods:
- Atherosclerotic (ApoE-/-) and wild-type (WT) mice underwent 70% liver clamping for 1 hour, followed by 6 hours of reperfusion.
- Liver damage, immune cell phenotype, and gene expression (IL-15, IRF-1) were analyzed.
Main Results:
- Atherosclerotic mice showed significantly greater liver damage (elevated AST/ALT, histological damage) compared to WT mice.
- Liver T and NK cells in atherosclerotic mice exhibited a more inflammatory phenotype.
- Upregulation of IL-15 and IRF-1 was observed in atherosclerotic mouse livers.
Conclusions:
- Atherosclerosis exacerbates hepatic IRI by modulating intrahepatic immunity.
- Increased IL-15 production, linked to IRF-1, activates liver NK and T cells, worsening liver damage in atherosclerotic conditions.
Background:
Abdominal aortic calcification (AAC) is associated with cardiovascular-related mortality, along with an elevated risk of coronary, cerebrovascular, and cardiovascular events. Notably, AAC is strongly associated with poor overall and recurrence free survival posthepatectomy for hepatocellular carcinoma. Despite the acknowledged significance of atherosclerosis in systemic inflammation, its response to ischemia/reperfusion injury (IRI) remains poorly elucidated. In this study, we aimed to clarify the impact of atherosclerosis on the liver immune system using a warm IRI mouse model.
Methods:
Injury was induced in an atherosclerotic mouse model (ApoE-/-) or C57BL/6J wild-type (WT) mice through 70% clamping for 1 hour and analyzed after 6 hours of reperfusion.
Results:
Elevated serum levels of aspartate and alanine aminotransferase, along with histological assessment, indicated considerable damage in the livers of ApoE-/- mice than that in WT mice. This indicates a substantial contribution of atherosclerosis to IRI. Furthermore, T and natural killer (NK) cells in ApoE-/- mouse livers displayed a more inflammatory phenotype than those in WT mouse livers. Reverse transcription-polymerase chain reaction analysis revealed a significant upregulation of interleukin (IL)-15 and its transcriptional regulator, interferon regulatory factor-1 (IRF-1) in ApoE-/- mouse livers compared with that in WT mouse livers.
Conclusions:
These findings suggest that in an atherosclerotic mouse model, atherosclerosis can mirror intrahepatic immunity, particularly activating liver NK and T cells through IL-15 production, thereby exacerbating hepatic damage. The upregulation of IL-15 expression is associated with IRF-1 overexpression.
Related Concept Videos
01:38Inflammation
01:30Atherosclerosis I: Introduction