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Published on: October 5, 2012
Expression of Apoptotic Markers Bcl-2 and Bax in the Vascular Wall
E A Klimentova1, I A Suchkov2, A V Shchulkin3
1Department of Cardiovascular, X-ray Endovascular, Operative Surgery, and Topographic Anatomy, Ryazan State Medical University, 9 Vysokovoltnaya St., Ryazan, 390026, Russia.
Insights
In advanced atherosclerosis obliterans, calcified plaques show reduced Bcl-2 and increased Bax protein levels, indicating apoptosis. Higher cholesterol correlates with increased Bax in these lesions.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Cardiovascular Research
Background:
- Atherosclerosis obliterans (AO) involves complex molecular changes in the vascular wall.
- Understanding the role of apoptosis-related proteins like Bcl-2 and Bax is crucial for AO progression.
- Serum cholesterol levels are a known risk factor for cardiovascular diseases, including AO.
Purpose of the Study:
- To investigate the expression levels of Bcl-2 and Bax proteins in the arterial wall of patients with stage III-IV AO.
- To determine the correlation between these protein levels and serum cholesterol.
- To analyze differences in protein expression based on atherosclerotic plaque echogenicity.
Main Methods:
- Analysis of vascular wall samples and atherosclerotic plaques from 32 patients undergoing surgery for stage III-IV AO.
- Measurement of Bcl-2 and Bax protein levels via homogenization and assay.
- Serum cholesterol level determination.
- Classification of atherosclerotic plaques based on ultrasonography (mixed vs. hyperechoic/calcified).
Main Results:
- In arterial walls with hyperechoic (calcified) plaques, Bcl-2 expression was significantly lower, and Bax expression was significantly higher compared to non-atherosclerotic controls.
- Patients with hyperechoic plaques showed reduced Bcl-2 and increased Bax compared to those with mixed echogenicity plaques.
- A positive correlation was observed between Bax expression and serum cholesterol levels (r=0.617) in patients with hyperechoic plaques.
Conclusions:
- Reduced Bcl-2 and increased Bax in calcified atherosclerotic plaques suggest activated apoptosis in advanced lesions.
- Elevated serum cholesterol is associated with increased pro-apoptotic Bax protein expression in these advanced atherosclerotic lesions.
- These findings highlight the role of apoptosis and cholesterol in the progression of severe atherosclerosis obliterans.
Abstract:
The aim of the study was to assess the levels of Всl-2 and Bax proteins in the vascular wall and their correlation with serum cholesterol in patients with stage III-IV atherosclerosis obliterans of lower limb arteries.
Materials And Methods:
The study included 32 patients with stage III-IV atherosclerosis obliterans of the lower limb. Samples of intraoperative material (all three layers of the vascular wall) including an atherosclerotic plaque (AP) were taken during primary open surgery on major leg arteries. As a control, we used samples of the arterial wall without visible signs of atherosclerosis. Based on AP ultrasonography, the patients were divided into two groups: with APs of mixed echogenicity and with hyperechoic (calcified) AP. The vascular samples were crushed and homogenized for further measurements of Всl-2 and Bax proteins; in a separate setup, cholesterol in blood serum was measured.
Results:
In patients without atherosclerotic changes, the level of the anti-apoptotic protein Bcl-2 in the arterial wall was 1.25 ng/mg, and that of the pro-apoptotic protein Bax - 4.7 ng/mg. In the case of APs of mixed echogenicity, the expression of Bcl-2 was 1.8 ng/mg (p=0.143) and that of Bax - 5.1 ng/mg (p=0.834), with no significant differences from AP-free vascular wall samples. In the arterial wall containing a heterogeneous calcified AP, the expression of Bcl-2 was 0.9 ng/mg (p=0.143), In contrast, the level of Bax was 6.8 ng/mg, which showed its significant increase as compared with the non-AP controls (p=0.02). In the cases with predominantly hyperechoic AP, the expression of Bcl-2 was significantly lower (p=0.036), and that of Bax - significantly higher (p=0.036) in comparison with AP of mixed echogenicity. In patients with hyperechoic AP, we found a negative correlation between the Bax and Bcl-2 values ( r=-0.315) and a positive correlation between the Bax expression and serum cholesterol (r=0.617).
Conclusion:
In arterial walls with hyperechoic (calcified) APs, the expression of anti-apoptotic protein Bcl-2 is reduced, and that of pro-apoptotic protein Bax is increased, which indicates the apoptosis activation in advanced atherosclerotic lesions. In patients with such APs, elevated cholesterol levels directly correlate with the increased expression of pro-apoptotic Bax protein (r=0.617).
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