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Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2023 Nov 20; Vol. 24 (22). Date of Electronic Publication: 2023 Nov 20. - Publication Year :
- 2023
-
Abstract
- 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.
- Subjects :
- Animals
Humans
Mice
Endothelial Cells metabolism
Glycoproteins genetics
Glycoproteins metabolism
Leucine metabolism
Mice, Knockout
Myocytes, Smooth Muscle metabolism
Plaque, Atherosclerotic metabolism
Atherosclerosis genetics
Atherosclerosis metabolism
Renal Insufficiency, Chronic metabolism
Vascular Calcification etiology
Vascular Calcification metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38003727
- Full Text :
- https://doi.org/10.3390/ijms242216537