N-Terminal Proteomics Reveals Distinct Protein Degradation Patterns in Different Types of Human Atherosclerotic Plaques
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| Název: | N-Terminal Proteomics Reveals Distinct Protein Degradation Patterns in Different Types of Human Atherosclerotic Plaques |
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| Autoři: | Lasse G. Lorentzen, Karin Yeung, Auguste Zitkeviciute, Karen C. Yang-Jensen, Nikolaj Eldrup, Jonas P. Eiberg, Michael J. Davies |
| Zdroj: | Lorentzen, L G, Yeung, K, Zitkeviciute, A, Yang-Jensen, K C, Eldrup, N, Eiberg, J P & Davies, M J 2025, ' N-Terminal Proteomics Reveals Distinct Protein Degradation Patterns in Different Types of Human Atherosclerotic Plaques ', Journal of Proteome Research, vol. 24, no. 1, pp. 144-157 . https://doi.org/10.1021/acs.jproteome.4c00548 |
| Informace o vydavateli: | American Chemical Society (ACS), 2024. |
| Rok vydání: | 2024 |
| Témata: | Atherosclerotic/metabolism, Peptide Fragments/metabolism, Proteomics, Male, Chromatography, Liquid, Peptide Hydrolases/metabolism, Extracellular Matrix/metabolism, Middle Aged, Plaque, Atherosclerotic, Peptide Fragments, Mass Spectrometry, Extracellular Matrix, Cross-Sectional Studies, Proteolysis, Humans, Plaque, Atherosclerotic/metabolism, Female, Carotid Stenosis, Proteomics/methods, Carotid Stenosis/metabolism, Plaque, Chromatography, Liquid, Aged, Peptide Hydrolases |
| Popis: | Atherosclerotic plaque rupture is a major cause of cardiovascular events. Plaque destabilization is associated with extracellular matrix (ECM) modification involving proteases which generate protein fragments with new N-termini. We hypothesized that rupture-prone plaques would contain elevated fragment levels, and their sequences would allow identification of active proteases and target proteins. Plaques from 21 patients who underwent surgery for symptomatic carotid artery stenosis were examined in an observational/cross-sectional study. Plaques were analyzed by liquid chromatography-mass spectrometry for the presence of N-terminal fragments. 33920 peptides were identified, with 17814 being N-terminal species. 5735 distinct N-terminal peptides were quantified and subjected to multidimensional scaling analysis and consensus clustering. These analyses indicated three clusters, which correlate with gross macroscopic plaque morphology (soft/mixed/hard), ultrasound classification (echolucent/echogenic), and the presence of hemorrhage/ulceration. Differences in the fragment complements are consistent with plaque-type-dependent turnover and degradation pathways. Identified peptides include signal and pro-peptides from synthesis and those from protein fragmentation. Sequence analysis indicates that targeted proteins include ECM species and responsible proteases (meprins, cathepsins, matrix metalloproteinases, elastase, and kallikreins). This study provides a large data set of peptide fragments and proteases present in plaques of differing stability. These species may have potential as biomarkers for improved atherosclerosis risk profiling. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.4c00548 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/39665830 https://curis.ku.dk/ws/files/432831587/N_Terminal_pro.pdf |
| Rights: | STM Policy #29 |
| Přístupové číslo: | edsair.doi.dedup.....a135912be96b176eea93a1e01a2fea5b |
| Databáze: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstrakt: | Atherosclerotic plaque rupture is a major cause of cardiovascular events. Plaque destabilization is associated with extracellular matrix (ECM) modification involving proteases which generate protein fragments with new N-termini. We hypothesized that rupture-prone plaques would contain elevated fragment levels, and their sequences would allow identification of active proteases and target proteins. Plaques from 21 patients who underwent surgery for symptomatic carotid artery stenosis were examined in an observational/cross-sectional study. Plaques were analyzed by liquid chromatography-mass spectrometry for the presence of N-terminal fragments. 33920 peptides were identified, with 17814 being N-terminal species. 5735 distinct N-terminal peptides were quantified and subjected to multidimensional scaling analysis and consensus clustering. These analyses indicated three clusters, which correlate with gross macroscopic plaque morphology (soft/mixed/hard), ultrasound classification (echolucent/echogenic), and the presence of hemorrhage/ulceration. Differences in the fragment complements are consistent with plaque-type-dependent turnover and degradation pathways. Identified peptides include signal and pro-peptides from synthesis and those from protein fragmentation. Sequence analysis indicates that targeted proteins include ECM species and responsible proteases (meprins, cathepsins, matrix metalloproteinases, elastase, and kallikreins). This study provides a large data set of peptide fragments and proteases present in plaques of differing stability. These species may have potential as biomarkers for improved atherosclerosis risk profiling. |
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| ISSN: | 15353907 15353893 |
| DOI: | 10.1021/acs.jproteome.4c00548 |