Leukocyte Cathepsin S Is a Potent Regulator of Both Cell and Matrix Turnover in Advanced Atherosclerosis
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| Název: | Leukocyte Cathepsin S Is a Potent Regulator of Both Cell and Matrix Turnover in Advanced Atherosclerosis |
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| Autoři: | de Nooijer, R., Bot, I., von der Thüsen, J.H., Leeuwenburgh, M.A., Overkleeft, H.S., Kraaijeveld, A.O., Dorland, R., van Santbrink, P.J., van Heiningen, S.H., Westra, M.M., Kovanen, P.T., Jukema, J.W., van der Wall, E.E., van Berkel, T.J.C., Shi, G.P., Biessen, E.A.L. |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 29:188-194 |
| Informace o vydavateli: | Ovid Technologies (Wolters Kluwer Health), 2009. |
| Rok vydání: | 2009 |
| Témata: | 0301 basic medicine, Apoptosis, Atherosclerosis, Elastic Tissue, Cathepsins, Extracellular Matrix, 3. Good health, Disease Models, Animal, Mice, 03 medical and health sciences, Cholesterol, Cell Movement, Leukocytes, Macrophages, Peritoneal, Animals, Diet, Atherogenic, Female, Collagen, Aorta, Cells, Cultured, Bone Marrow Transplantation, Cell Proliferation, Foam Cells |
| Popis: | Objective— A dysbalance of proteases and their inhibitors is instrumental in remodeling of atherosclerotic plaques. One of the proteases implicated in matrix degradation is cathepsin-S (CatS). To address its role in advanced lesion composition, we generated chimeric LDLr −/− mice deficient in leukocyte CatS by transplantation with CatS −/− ×LDLr −/− or with LDLr −/− bone marrow and administered a high-fat diet. Methods and Results— No difference in aortic root lesion size could be detected between CatS +/+ and CatS −/− chimeras. However, leukocyte CatS deficiency markedly changed plaque morphology and led to a dramatic reduction in necrotic core area by 77% and an abundance of large foam cells. Plaques of CatS −/− chimeras contained 17% more macrophages, 62% less SMCs, and 33% less intimal collagen. The latter two could be explained by a reduced number of elastic lamina fractures. Moreover, macrophage apoptosis was reduced by 60% with CatS deficiency. In vitro, CatS was found to be involved in cholesterol metabolism and in macrophage apoptosis in a collagen and fibronectin matrix. Conclusion— Leukocyte CatS deficiency results in considerably altered plaque morphology, with smaller necrotic cores, reduced apoptosis, and decreased SMC content and collagen deposition and may thus be critical in plaque stability. |
| Druh dokumentu: | Article |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.108.181578 |
| Přístupová URL adresa: | https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.108.181578 https://pubmed.ncbi.nlm.nih.gov/19095996 https://hdl.handle.net/11245/1.320411 https://doi.org/10.1161/ATVBAHA.108.181578 https://dare.uva.nl/personal/pure/en/publications/leukocyte-cathepsin-s-is-a-potent-regulator-of-both-cell-and-matrix-turnover-in-advanced-atherosclerosis(d692b5e1-3ec3-41b5-8395-fdfaf9bcb226).html |
| Přístupové číslo: | edsair.doi.dedup.....c1cfdd062ab4c67cd41bb96da9d0d7f9 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Objective— A dysbalance of proteases and their inhibitors is instrumental in remodeling of atherosclerotic plaques. One of the proteases implicated in matrix degradation is cathepsin-S (CatS). To address its role in advanced lesion composition, we generated chimeric LDLr −/− mice deficient in leukocyte CatS by transplantation with CatS −/− ×LDLr −/− or with LDLr −/− bone marrow and administered a high-fat diet. Methods and Results— No difference in aortic root lesion size could be detected between CatS +/+ and CatS −/− chimeras. However, leukocyte CatS deficiency markedly changed plaque morphology and led to a dramatic reduction in necrotic core area by 77% and an abundance of large foam cells. Plaques of CatS −/− chimeras contained 17% more macrophages, 62% less SMCs, and 33% less intimal collagen. The latter two could be explained by a reduced number of elastic lamina fractures. Moreover, macrophage apoptosis was reduced by 60% with CatS deficiency. In vitro, CatS was found to be involved in cholesterol metabolism and in macrophage apoptosis in a collagen and fibronectin matrix. Conclusion— Leukocyte CatS deficiency results in considerably altered plaque morphology, with smaller necrotic cores, reduced apoptosis, and decreased SMC content and collagen deposition and may thus be critical in plaque stability. |
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| ISSN: | 15244636 10795642 |
| DOI: | 10.1161/atvbaha.108.181578 |