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Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Age and gender effects on apoptosis in the human coronary arterial wall
Jacques Boddaert1, Ziad Mallat, Paul Fornes
1INSERM U-541, IFR Circulation, Hôpital Lariboisière, Paris, France. jacques.boddaert@psl.ap-hop-paris.fr
Abstract:
The relationship between aging and apoptosis remains unclear. We wondered whether apoptosis could be enhanced in arterial aging in the absence of overt or advanced arterial disease. Apoptosis-related proteins were investigated using three methods: TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique, active cysteine-dependant aspartate specific proteases (caspase)-3 and poly ADP-ribose polymerase (PARP) in coronary arteries of human subjects ranging from 25 to 92 years. We found no significant correlation between age and the apoptotic index using the three methods. The percentage of active caspase-3 positive cells was found to be significantly higher in men than in women (9.11 +/- 12.3 cells/mm(2) versus 2.01 +/- 4.55 cells/mm(2), respectively, p = 0.017). These sex-related differences did not reach statistical significance using TUNEL (9.93 +/- 17 and 2.61 +/- 4.58 cells/mm(2), p = 0.32) and PARP methods (3.42 +/- 7.74 and 0.86 +/- 0.95 cells/mm(2), p < 0.49). This is the first report of detection of apoptotic cells in the human arterial wall in adult subjects free from arterial diseases. Apoptosis is an attractive hypothesis to account for organ aging, but our study suggests that apoptosis is not a key factor in aging of the arterial wall.
Insights
Apoptosis, programmed cell death, does not significantly increase with arterial aging in healthy adults. However, active caspase-3 levels were higher in men, suggesting sex-specific differences in arterial cells.
Area of Science:
- Cardiovascular Science
- Cell Biology
- Aging Research
Background:
- The role of apoptosis (programmed cell death) in arterial aging is not well understood.
- Investigating apoptosis in the arterial wall is crucial for understanding aging processes.
Purpose of the Study:
- To determine if apoptosis is enhanced in the aging human arterial wall, independent of disease.
- To explore potential sex-related differences in arterial apoptosis.
Main Methods:
- Examined apoptosis markers including TUNEL, active caspase-3, and PARP in coronary arteries from adults aged 25-92.
- Utilized immunohistochemistry and biochemical assays to quantify apoptotic cells and proteins.
Main Results:
- No significant correlation was found between chronological age and apoptotic index across all three methods.
- Significantly higher levels of active caspase-3 positive cells were observed in men compared to women (p=0.017).
- Sex-related differences in apoptosis were not statistically significant for TUNEL and PARP methods.
Conclusions:
- This study provides the first evidence of apoptotic cells in the healthy adult human arterial wall.
- Apoptosis does not appear to be a primary driver of arterial aging in the absence of overt disease.
- Sex-specific differences in arterial apoptosis warrant further investigation.
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