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Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
TMT-based quantitative proteomic profiling of human monocyte-derived macrophages and foam cells
Yali Zhang1,2, Yu Fu2, Linying Jia1,2
1Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Centre, No. 76, Yanta West Road, Xi'an, 710061, Shaanxi, China.
Insights
This study reveals that during foam cell formation, crucial for atherosclerosis, cholesterol metabolism increases while immune responses decrease. Key proteins in the endoplasmic reticulum and lysosomes drive this transformation.
Area of Science:
- Proteomics
- Molecular Biology
- Cardiovascular Research
Background:
- Atherosclerosis, a major cause of cardiovascular disease, involves macrophage-to-foam cell transformation.
- Understanding the molecular mechanisms of foam cell formation is critical for atherosclerosis research.
Purpose of the Study:
- To explore the molecular mechanisms of foam cell formation by identifying differentially expressed proteins.
- To investigate proteome profile changes during macrophage transformation into foam cells.
Main Methods:
- Human peripheral blood mononuclear cells were differentiated into macrophages and then transformed into foam cells using oxidized low-density lipoprotein.
- Tandem mass tag (TMT) labeling and mass spectrometry were employed to analyze proteome profiles.
Main Results:
- 5146 quantifiable proteins were identified, with 1515 and 182 differentially expressed proteins (DEPs) in macrophages/monocytes and foam cells/macrophages, respectively.
- Upregulated DEPs in foam cells were linked to cholesterol metabolism, while downregulated DEPs were associated with immune response.
- Key DEPs involved in foam cell formation were concentrated in lysosomes and the endoplasmic reticulum.
Conclusions:
- Proteomics analysis indicates upregulated cholesterol metabolism and suppressed immune response in foam cells.
- DEPs within the endoplasmic reticulum and lysosomes are suggested as potential key drivers of foam cell formation.
- These findings provide a foundation for identifying proteins involved in macrophage-to-foam cell transformation in atherosclerosis.
Background:
Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified.
Methods:
Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles.
Results:
Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum.
Conclusions:
Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells.
