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Published on: August 16, 2019
Reduced expression of NLRP3 and MEFV in human ischemic heart tissue
Cecilia Hermansson1, Annika Lundqvist, Carina Wasslavik
1Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Abstract:
The innate immune system and, in particular, activation of the multi-protein complex known as the inflammasome complex are involved in ischemic injury in myocardial cells. The nucleotide-binding leucine-rich repeat-containing pyrin receptor 3 (NLRP3) inflammasome has been linked to inflammation and NLRP3 is especially important for increased inflammation in atherosclerosis, which may lead to myocardial infarction. Here we investigated how inflammasome molecules are affected in human ischemic heart tissue. Surprisingly the important member of the inflammasome complex, NLRP3, displayed markedly decreased levels in human ischemic heart tissue compared with non ischemic control heart tissue. However, subsequent gene analysis revealed mutations in NLRP3 in human ischemic heart tissues but not in non-ischemic control tissue. Gene polymorphisms in the NLRP3 inflammasome have been shown to be associated with increased IL-1β and IL-18 production and severe inflammation. The autoinflammatory disorder familial Mediterranean fever (FMF) is associated with decreased expression of the Mediterranean fever gene (MEFV) and increased inflammation. We also observed reduced expression of MEFV in ischemic versus non-ischemic heart tissue. Further analyses showed a mutation in MEFV in human ischemic heart tissue but not in non-ischemic control tissue. Our data show that defects in the inflammasome and associated proteins may be involved in promoting ischemic heart disease.
Insights
Defects in the NLRP3 inflammasome and MEFV gene, identified through mutations in human ischemic heart tissue, may promote heart disease. These findings highlight a potential link between inflammasome dysfunction and myocardial infarction risk.
Area of Science:
- Immunology
- Cardiovascular Biology
- Genetics
Background:
- The innate immune system, particularly inflammasomes, plays a role in myocardial ischemic injury.
- The NLRP3 inflammasome is implicated in atherosclerosis and myocardial infarction.
- Understanding inflammasome involvement in ischemic heart disease is crucial.
Purpose of the Study:
- To investigate the impact of inflammasome molecules in human ischemic heart tissue.
- To explore the relationship between NLRP3 inflammasome defects and ischemic heart disease.
- To examine the role of the Mediterranean fever gene (MEFV) in this context.
Main Methods:
- Analysis of NLRP3 and MEFV expression in human ischemic and non-ischemic heart tissues.
- Gene sequencing to identify mutations in NLRP3 and MEFV.
- Comparison of molecular findings between ischemic and control heart tissues.
Main Results:
- NLRP3 inflammasome member NLRP3 showed decreased levels in ischemic heart tissue.
- Mutations in NLRP3 were found in human ischemic heart tissues but not in controls.
- Reduced MEFV expression and MEFV mutations were observed in ischemic heart tissue.
Conclusions:
- Defects in the inflammasome complex and associated proteins, including NLRP3 and MEFV, are associated with human ischemic heart disease.
- Mutations in NLRP3 and MEFV may contribute to the pathogenesis of ischemic heart disease.
- These findings suggest a novel mechanism involving inflammasome dysfunction in myocardial infarction.