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Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
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Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death
Carlos Silvestre-Roig1,2,3, Quinte Braster4,5,6, Kanin Wichapong7
1Institute for Cardiovascular Prevention (IPEK), LMU München, Munich, Germany. carlos.silvestre@med.uni-muenchen.de.
Nature
|May 3, 2019
Summary
Extracellular histone H4 causes smooth muscle cell death and arterial damage in atherosclerosis. Neutralizing histone H4 prevents cell death, stabilizing atherosclerotic lesions and offering a potential therapeutic target for chronic vascular disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cell Death Mechanisms
Background:
- Chronic inflammation is a significant global health burden.
- Non-programmed cell death contributes to chronic inflammation, but its instigation and mediators are unclear.
- Atherosclerosis, a leading cause of mortality, involves arterial inflammation and plaque instability.
Purpose of the Study:
- To investigate the role of extracellular histone H4 in smooth muscle cell death and inflammation in atherosclerosis.
- To identify cellular and molecular mediators of inflammation in vascular disease.
- To explore potential therapeutic strategies targeting histone H4.
Main Methods:
- Utilized mouse models of atherosclerosis.
- Investigated the interaction between extracellular histone H4 and smooth muscle cells (SMCs).
- Analyzed neutrophil extracellular trap (NET) formation and histone H4 release.
- Assessed the effect of histone H4 neutralization on SMC death and plaque stability.
Main Results:
- Extracellular histone H4 mediates membrane lysis of SMCs, triggering arterial tissue damage and inflammation.
- Activated SMCs attract neutrophils, leading to NET ejection containing nuclear proteins like histone H4.
- Histone H4 binding to SMCs causes cell death and plaque destabilization; its neutralization prevents SMC death and stabilizes lesions.
Conclusions:
- Identified a novel form of leukocyte-instigated cell death in chronic vascular disease.
- Extracellular histone H4 is a key mediator of SMC death and atherosclerotic plaque instability.
- Targeting extracellular histone H4 offers a promising therapeutic avenue for atherosclerosis and related chronic vascular diseases.
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