Leucine-Rich Alpha-2 Glycoprotein 1 Accumulates in Complicated Atherosclerosis and Promotes Calcification

被引:3
|
作者
Grzesiak, Lucile [1 ,2 ]
Amaya-Garrido, Ana [1 ,2 ]
Feuillet, Guylene [1 ,2 ]
Malet, Nicole [1 ,2 ]
Swiader, Audrey [1 ,2 ]
Sarthou, Marie-Kerguelen [1 ,2 ]
Wahart, Amandine [1 ,2 ]
Ramel, Damien [1 ,2 ]
Gayral, Stephanie [1 ,2 ]
Schanstra, Joost Peter [1 ,2 ]
Klein, Julie [1 ,2 ]
Laffargue, Muriel [1 ,2 ]
机构
[1] INSERM, U1297, Inst Cardiovasc & Metab Dis, F-31432 Toulouse, France
[2] Univ Toulouse III Paul Sabatier, Dept Biol, F-31062 Toulouse, France
基金
欧盟地平线“2020”;
关键词
atherosclerosis; vascular smooth muscle cell; calcification; LRG1; ARTERIAL STIFFNESS; CARDIOVASCULAR RISK; DISEASE; MECHANISMS; LRG1; PROGRESSION; ENDOGLIN; RUPTURE; MARKER; IMPACT;
D O I
10.3390/ijms242216537
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-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.
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页数:12
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