Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types
Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial inf...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Matrix Biology Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590028524000012 |
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| author | Lasse G. Lorentzen Karin Yeung Nikolaj Eldrup Jonas P. Eiberg Henrik H. Sillesen Michael J. Davies |
| author_facet | Lasse G. Lorentzen Karin Yeung Nikolaj Eldrup Jonas P. Eiberg Henrik H. Sillesen Michael J. Davies |
| author_sort | Lasse G. Lorentzen |
| collection | DOAJ |
| description | Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis. |
| first_indexed | 2024-03-08T00:08:47Z |
| format | Article |
| id | doaj.art-0a9a9102d7554e10bb6b3f4daa17b5c5 |
| institution | Directory Open Access Journal |
| issn | 2590-0285 |
| language | English |
| last_indexed | 2024-03-08T00:08:47Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Matrix Biology Plus |
| spelling | doaj.art-0a9a9102d7554e10bb6b3f4daa17b5c52024-02-17T06:42:09ZengElsevierMatrix Biology Plus2590-02852024-02-0121100141Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque typesLasse G. Lorentzen0Karin Yeung1Nikolaj Eldrup2Jonas P. Eiberg3Henrik H. Sillesen4Michael J. Davies5Department of Biomedical Sciences, Panum Institute, University of Copenhagen, DenmarkDepartment of Vascular Surgery, Heart Centre, University Hospital Copenhagen - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DenmarkDepartment of Vascular Surgery, Heart Centre, University Hospital Copenhagen - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DenmarkDepartment of Vascular Surgery, Heart Centre, University Hospital Copenhagen - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Copenhagen Academy for Medical Education and Simulation (CAMES), Capital Region of Denmark, Copenhagen, DenmarkDepartment of Vascular Surgery, Heart Centre, University Hospital Copenhagen - Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, DenmarkDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, Denmark; Corresponding author.Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.http://www.sciencedirect.com/science/article/pii/S2590028524000012AtherosclerosisExtracellular matrixProteomicsCarotid endarterectomyCarotid artery stenosis |
| spellingShingle | Lasse G. Lorentzen Karin Yeung Nikolaj Eldrup Jonas P. Eiberg Henrik H. Sillesen Michael J. Davies Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types Matrix Biology Plus Atherosclerosis Extracellular matrix Proteomics Carotid endarterectomy Carotid artery stenosis |
| title | Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| title_full | Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| title_fullStr | Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| title_full_unstemmed | Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| title_short | Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| title_sort | proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types |
| topic | Atherosclerosis Extracellular matrix Proteomics Carotid endarterectomy Carotid artery stenosis |
| url | http://www.sciencedirect.com/science/article/pii/S2590028524000012 |
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