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Updated: Jun 20, 2026
06:47
Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Macrophage apoptosis in advanced atherosclerosis
Ira Tabas1, Tracie Seimon, Jenelle Timmins
1Department of Medicine, Columbia University Medical Center, New York, New York, USA. iat1@columbia.edu
Annals of the New York Academy of Sciences
|September 16, 2009
Summary
Endoplasmic reticulum (ER) stress triggers macrophage apoptosis in advanced atherosclerosis, leading to plaque necrosis and vascular events. This ER stress, combined with pattern recognition receptor activation, drives plaque vulnerability and offers potential therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Cellular Stress Response
- Immunopathology
Background:
- Advanced atherosclerosis involves plaque necrosis and acute atherothrombotic events.
- Macrophage apoptosis and impaired clearance of dead cells drive plaque necrosis.
- Endoplasmic reticulum (ER) stress, via the unfolded protein response (UPR), is central to macrophage apoptosis in atherosclerosis.
Purpose of the Study:
- To elucidate the mechanisms of macrophage apoptosis in advanced atherosclerotic plaques.
- To investigate the role of ER stress and pattern recognition receptors (PRRs) in plaque vulnerability.
- To identify potential therapeutic targets for preventing atherothrombotic events.
Main Methods:
- Analysis of human atherosclerotic lesions for UPR activation markers.
- Studies using genetically altered mice to assess the impact of ER stress and PRR activation.
- Investigation of apoptotic signaling pathways including CHOP, CaMKII, STAT1, Fas, and mitochondrial pathways.
Main Results:
- UPR activation in advanced human lesions correlates with plaque vulnerability and macrophage apoptosis.
- ER stress and PRR activation are causative for macrophage apoptosis and plaque necrosis in mouse models.
- Key apoptotic pathways activated by ER stress include CHOP, CaMKII, STAT1, Fas, and mitochondrial cytochrome c release.
Conclusions:
- ER stress-induced macrophage apoptosis is a critical cellular event in the progression of atherosclerosis from benign to vulnerable plaques.
- Combined ER stress and PRR activation are key drivers of plaque necrosis.
- Understanding these mechanisms may lead to novel therapies for preventing clinical atherothrombotic events.
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