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Regulation of programmed cell death or apoptosis in atherosclerosis
1Cardiovascular and Pulmonary Research Institute, Allegheny University of the Health Sciences, Pittsburgh, PA 15212, USA.
Insights
Atherosclerosis involves abnormal cell death (apoptosis) in arterial plaques. Understanding apoptosis regulation is key to developing new treatments for heart attack and stroke.
Area of Science:
- Cardiovascular Science
- Cell Biology
- Immunology
Background:
- Atherosclerosis is characterized by arterial intimal thickening due to cell and lipid accumulation.
- Apoptosis, or programmed cell death, is crucial for tissue development and turnover.
- Increased apoptosis is observed in atherosclerotic lesions, involving vascular and immune cells.
Purpose of the Study:
- To explore the role of apoptosis in the development and progression of atherosclerosis.
- To identify molecular mechanisms regulating vascular apoptosis in atherosclerotic lesions.
Main Methods:
- Analysis of apoptotic processes in human and animal atherosclerotic models.
- Investigation of the involvement of immune cells and their secreted cytokines (e.g., TNF, IL-1, IFN-gamma).
- Examination of death-regulating genes (e.g., Fas/Fas ligand, caspases, p53, c-myc) in vascular cells.
Main Results:
- Apoptosis plays a significant role in atherosclerotic lesion development and tissue turnover.
- Pro-inflammatory cytokines from immune cells may induce apoptosis in vascular smooth muscle cells.
- Dysregulation of apoptosis (attenuation or acceleration) impacts lesion cellularity and plaque stability.
Conclusions:
- Molecular mechanisms regulating vascular apoptosis are critical in atherosclerosis.
- Targeting apoptosis pathways offers a potential therapeutic strategy for atherosclerosis and its complications like heart attack and stroke.
Abstract:
Intimal thickening caused by accumulation of cells, lipids, and connective tissue characterizes atherosclerosis, an arterial disease that leads to cardiac and cerebral infarction. Apoptosis, or genetically programmed cell death, is important for the development and morphogenesis of organs and tissues. As in other tissues, cells of cardiovascular tissues can undergo apoptosis. Increased apoptosis has been found in both human and animal atherosclerotic lesions, mediating tissue turnover and lesion development. In addition to vascular cells, many activated immune cells, mainly macrophages and T cells, are present in atherosclerotic lesions, where these cells produce biologically active substances such as the proinflammatory cytokines tumor necrosis factor, interleukin-1 (IL-1), and interferon-gamma. Simultaneous exposure to these cytokines may trigger apoptosis of vascular smooth muscle cells. The products of death-regulating genes including Fas/Fas ligand, members of IL-1 beta cysteinyl protease (caspase) family, the tumor suppressive gene p53, and the protooncogene c-myc have been found in vascular cells and may participate in the regulation of vascular apoptosis during the development of atherosclerosis. Abnormal occurrence of apoptosis may take place in atherosclerotic lesions, including attenuation or acceleration of the apoptotic death process. The former may cause an increase in the cellularity of the lesions, and the latter can reduce cellular components important for maintaining the integrity and stability of the plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of patients with atherosclerosis and its major complications, heart attack and stroke.