Related Experiment Videos
Apoptosis in atherosclerosis: beneficial or detrimental?
1Department of Pathology, A.Z. Middelheim, Antwerp, Belgium. mark.kockx@uia.ua.ac.be
Insights
Apoptosis, or programmed cell death, in atherosclerosis is detrimental, potentially causing plaque rupture and thrombosis. Lipid lowering therapies may reduce this cell death, aiding plaque stabilization.
Area of Science:
- Cardiovascular Biology
- Cellular Pathology
Background:
- Apoptotic cell death occurs in atherosclerotic plaques, involving macrophages and smooth muscle cells.
- The role of apoptosis in atherosclerosis varies with plaque stage, location, and cell type.
Purpose of the Study:
- To investigate the significance of apoptotic cell death in atherosclerotic plaque stability.
- To explore the impact of lipid-lowering on apoptosis within atherosclerotic plaques.
Main Methods:
- Analysis of apoptotic cell death in atherosclerotic plaques.
- Correlation of apoptosis with DNA synthesis/repair and plaque characteristics.
- Evaluation of apoptosis changes following lipid-lowering interventions.
Main Results:
- Smooth muscle cell apoptosis occurs in less cellular regions and is not linked to DNA repair.
- Macrophage apoptosis is associated with DNA synthesis/repair.
- Unscavenged apoptotic cells can activate thrombin, promoting thrombosis.
- Apoptosis decreases following lipid-lowering therapy.
Conclusions:
- Apoptosis in atherosclerosis is generally detrimental, potentially leading to plaque rupture and thrombosis.
- Smooth muscle cell loss due to apoptosis compromises plaque stability.
- Effective clearance of apoptotic bodies may be crucial for plaque stability.
- Lipid-lowering interventions show potential in stabilizing atherosclerotic plaques by reducing apoptosis.
Abstract:
Several groups have demonstrated apoptotic cell death in atherosclerotic plaques. The significance of apoptosis in atherosclerosis depends on the stage of the plaque, localization and the cell types involved. Both macrophages and smooth muscle cells undergo apoptosis in atherosclerotic plaques. Apoptosis of macrophages is mainly present in regions showing signs of DNA synthesis/repair. Smooth muscle cell apoptosis is mainly present in less cellular regions and is not associated with DNA synthesis/repair. Even in early stages of atherosclerosis smooth muscle cells become susceptible to undergoing apoptosis since they increase different pro-apoptotic factors. Moreover, recent data indicate that smooth muscle cells may be killed by activated macrophages. The loss of the smooth muscle cells can be detrimental for plaque stability since most of the interstitial collagen fibers, which are important for the tensile strength of the fibrous cap, are produced by SMC. Apoptosis of macrophages could be beneficial for plaque stability if apoptotic bodies are removed. Apoptotic cells that are not scavenged in the plaque activate thrombin which could further induce intraplaque thrombosis. It can be concluded that apoptosis in the primary atherosclerosis is detrimental since it could lead to plaque rupture and thrombosis. Recent data of our group indicate that apoptosis decreases after lipid lowering which could be important in our understanding of the cell biology of plaque stabilization.