Functional pathways associated with human carotid atheroma: a proteomics analysis.

Advances in large-scale analysis are becoming very useful in understanding health and disease. Here, we used high-throughput mass spectrometry to identify differentially expressed proteins between early and advanced lesions. Carotid endarterectomy samples were collected and dissected into early and advanced atherosclerotic lesion portions. Proteins were extracted and subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Differentially expressed proteins were identified and verified using multiple reaction monitoring (MRM), on which advanced systems biology and enrichment analyses were performed. The identified proteins were further compared to the transcriptomic data of 32 paired samples obtained from early and advanced atherosclerotic lesions. A total of 95 proteins were upregulated, and 117 proteins were downregulated in advanced lesions compared to early atherosclerotic lesions (p < 0.05). The upregulated proteins were associated with proatherogenic processes, whereas downregulated proteins were involved in extracellular matrix organization and vascular smooth muscle cytoskeleton. Many of the identified proteins were linked to various "upstream regulators", among which TGFβ had the highest connections. Specifically, a total of 19 genes were commonly upregulated, and 30 genes were downregulated at the mRNA and protein levels. These genes were involved in vascular smooth muscle cell activity, for which enriched transcription factors were identified. This study deciphers altered pathways in atherosclerosis and identifies upstream regulators that could be candidate targets for treatment.