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Proteomic analysis of human vessels: application to atherosclerotic plaques
Mari Carmen Duran1, Sebastian Mas, Jose Luis Martin-Ventura
1Department Immunology, Fundación Jímenez Díaz, Madrid, Spain.
Insights
Atherosclerosis plaque complexity correlates with increased protein secretion. Analyzing proteins secreted by carotid artery plaques reveals more proteins are released as lesions become more complicated, suggesting specific protein involvement.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Vascular Medicine
Background:
- Atherosclerosis involves complex arterial wall lesions, leading to myocardial infarction and stroke.
- Heterogeneous plaque composition makes whole-lesion proteomic analysis challenging.
- Studying secreted proteins offers insight into plaque development and complexity.
Purpose of the Study:
- To investigate the proteomic differences in proteins secreted by human carotid atherosclerotic plaques.
- To correlate plaque complexity with the profile of secreted proteins.
Main Methods:
- Human carotid artery segments (normal, noncomplicated plaque, complicated plaque with thrombus) were obtained via endarterectomy.
- Segments were cultured in protein-free medium to collect secreted proteins (supernatants).
- Secreted proteins were analyzed using two-dimensional gel electrophoresis.
Main Results:
- Normal artery segments secreted a moderate number of proteins (42 spots).
- Segments with noncomplicated plaques showed a marked increase in secreted proteins (154 spots).
- Segments with complicated plaques and thrombus exhibited the highest number of secreted proteins (202 spots).
Conclusions:
- The number of secreted proteins increases with atherosclerotic lesion complexity.
- This suggests the production of specific proteins related to the progression and severity of atherosclerotic lesions.
- Secreted protein analysis is a valuable approach to understanding atherosclerosis pathogenesis.
Abstract:
Atherosclerosis is a chronic disease that affects medium and large arteries. This process originates from the interaction between cells of the arterial wall, lipoproteins and inflammatory cells, leading to the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in acute clinical complications such as myocardial infarction and stroke. Owing to the heterogeneous cellular composition of the plaques, a proteomic analysis of the whole lesion is not appropriate. Therefore, we have studied the proteins secreted by human carotid atherosclerotic plaques, obtained by endarterectomy. Normal artery segments and different regions of the surgical pieces (noncomplicated plaque, complicated plaque with thrombus) were cultured in protein-free medium and the secreted proteins (supernatants) analyzed by two-dimensional gel electrophoresis. Normal artery segments secreted a moderate number of proteins (42 spots). However in the two-dimensional (2-D) gels (pH 3-10) of segments bearing a plaque, the number of spots increased markedly (154). The number of spots also increased (202) in the 2-D gels of artery segments with a ruptured plaque and thrombus. Thus, the more complicated the lesion, the higher the number of secreted proteins, suggesting the production of specific proteins relating to the complexity of the atherosclerotic lesion.