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Published on: March 7, 2019
Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass
Nicole Hansmeier1, Josef Buttigieg2, Pankaj Kumar2
1Department of Biology/Chemistry, Division of Microbiology, University of Osnabrück , Barbarastrasse 11, 49076 Osnabrück, Germany.
Insights
This study provides a comprehensive proteome analysis of atherosclerotic plaques, revealing key proteins involved in vascular remodeling. It highlights a decrease in smooth muscle cell markers, suggesting their central role in advanced plaque structure.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Pathology
Background:
- Atherosclerosis is a chronic inflammatory disease and a leading cause of cardiovascular events.
- Vascular remodeling, driven by numerous proteins, is a hallmark of atherosclerosis.
- Plaque composition significantly influences cardiovascular and neurological symptoms.
Purpose of the Study:
- To create quantitative proteome profiles of advanced human atherosclerotic plaque tissue.
- To identify key proteins involved in vascular remodeling within atherosclerotic plaques.
- To compare protein composition between mature plaques and proximal arterial tissue.
Main Methods:
- Quantitative proteome profiling using a data-independent approach.
- Analysis of advanced plaque tissues from six male patients undergoing carotid endarterectomy.
- Identification and quantification of over 4000 proteins.
Main Results:
- Identified 4181 proteins with 45% average protein coverage.
- Found 20 proteins enriched and 52 proteins with lower quantities in mature plaques compared to proximal tissue.
- Observed increased abundance of extracellular matrix proteins (e.g., biglycan, lumican) and decreased cytoskeletal markers for smooth muscle cells (SMCs).
Conclusions:
- This study offers the most comprehensive quantitative assessment of mature human atherosclerotic plaque tissue to date.
- The findings indicate a significant decrease in contractile SMC markers within advanced plaques.
- Smooth muscle cells play a central role in the structural integrity of advanced atherosclerotic plaques.
Abstract:
Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.
