Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification
Atherosclerosis is the primary cause of cardiovascular disease. The development of plaque complications, such as calcification and neo-angiogenesis, strongly impacts plaque stability and is a good predictor of mortality in patients with atherosclerosis. Despite well-known risk factors of plaque comp...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16537 |
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| author | Lucile Grzesiak Ana Amaya-Garrido Guylène Feuillet Nicole Malet Audrey Swiader Marie-Kerguelen Sarthou Amandine Wahart Damien Ramel Stéphanie Gayral Joost Peter Schanstra Julie Klein Muriel Laffargue |
| author_facet | Lucile Grzesiak Ana Amaya-Garrido Guylène Feuillet Nicole Malet Audrey Swiader Marie-Kerguelen Sarthou Amandine Wahart Damien Ramel Stéphanie Gayral Joost Peter Schanstra Julie Klein Muriel Laffargue |
| author_sort | Lucile Grzesiak |
| collection | DOAJ |
| description | Atherosclerosis is the primary cause of cardiovascular disease. The development of plaque complications, such as calcification and neo-angiogenesis, strongly impacts plaque stability and is a good predictor of mortality in patients with atherosclerosis. Despite well-known risk factors of plaque complications, such as diabetes mellitus and chronic kidney disease, the mechanisms involved are not fully understood. We and others have identified that the concentration of circulating leucine-rich α-2 glycoprotein 1 (LRG1) was increased in diabetic and chronic kidney disease patients. Using apolipoprotein E knockout mice (ApoE−/−) (fed with Western diet) that developed advanced atherosclerosis and using human carotid endarterectomy, we showed that LRG1 accumulated into an atherosclerotic plaque, preferentially in calcified areas. We then investigated the possible origin of LRG1 and its functions on vascular cells and found that LRG1 expression was specifically enhanced in endothelial cells via inflammatory mediators and not in vascular smooth muscle cells (VSMC). Moreover, we identified that LRG1 was able to induce calcification and SMAD1/5-signaling pathways in VSMC. In conclusion, our results identified for the first time that LRG1 is a direct contributor to vascular calcification and suggest a role of this molecule in the development of plaque complications in patients with atherosclerosis. |
| first_indexed | 2024-03-09T16:45:06Z |
| format | Article |
| id | doaj.art-86d5dc4a05c34522bfa27192312b8786 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:06Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-86d5dc4a05c34522bfa27192312b87862023-11-24T14:48:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221653710.3390/ijms242216537Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes CalcificationLucile Grzesiak0Ana Amaya-Garrido1Guylène Feuillet2Nicole Malet3Audrey Swiader4Marie-Kerguelen Sarthou5Amandine Wahart6Damien Ramel7Stéphanie Gayral8Joost Peter Schanstra9Julie Klein10Muriel Laffargue11Institut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM), U1297, Institute of Cardiovascular and Metabolic Disease, 31432 Toulouse, FranceAtherosclerosis is the primary cause of cardiovascular disease. The development of plaque complications, such as calcification and neo-angiogenesis, strongly impacts plaque stability and is a good predictor of mortality in patients with atherosclerosis. Despite well-known risk factors of plaque complications, such as diabetes mellitus and chronic kidney disease, the mechanisms involved are not fully understood. We and others have identified that the concentration of circulating leucine-rich α-2 glycoprotein 1 (LRG1) was increased in diabetic and chronic kidney disease patients. Using apolipoprotein E knockout mice (ApoE−/−) (fed with Western diet) that developed advanced atherosclerosis and using human carotid endarterectomy, we showed that LRG1 accumulated into an atherosclerotic plaque, preferentially in calcified areas. We then investigated the possible origin of LRG1 and its functions on vascular cells and found that LRG1 expression was specifically enhanced in endothelial cells via inflammatory mediators and not in vascular smooth muscle cells (VSMC). Moreover, we identified that LRG1 was able to induce calcification and SMAD1/5-signaling pathways in VSMC. In conclusion, our results identified for the first time that LRG1 is a direct contributor to vascular calcification and suggest a role of this molecule in the development of plaque complications in patients with atherosclerosis.https://www.mdpi.com/1422-0067/24/22/16537atherosclerosisvascular smooth muscle cellcalcificationLRG1 |
| spellingShingle | Lucile Grzesiak Ana Amaya-Garrido Guylène Feuillet Nicole Malet Audrey Swiader Marie-Kerguelen Sarthou Amandine Wahart Damien Ramel Stéphanie Gayral Joost Peter Schanstra Julie Klein Muriel Laffargue Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification International Journal of Molecular Sciences atherosclerosis vascular smooth muscle cell calcification LRG1 |
| title | Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification |
| title_full | Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification |
| title_fullStr | Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification |
| title_full_unstemmed | Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification |
| title_short | Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification |
| title_sort | leucine rich alpha 2 glycoprotein 1 accumulates in complicated atherosclerosis and promotes calcification |
| topic | atherosclerosis vascular smooth muscle cell calcification LRG1 |
| url | https://www.mdpi.com/1422-0067/24/22/16537 |
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