LRG1 accumulates in atherosclerotic plaques, preferentially in calcified areas, and directly induces calcification and SMAD1/5-signaling pathways in vascular smooth muscle cells.
LRG1 accumulates in atherosclerotic plaques and directly promotes vascular calcification via SMAD1/5 signaling, suggesting a role in plaque complications.
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.
Grzesiak et al. (Mon,) conducted a other in Atherosclerosis. Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) was evaluated on Vascular calcification and SMAD1/5-signaling pathway activation. LRG1 accumulates in atherosclerotic plaques, preferentially in calcified areas, and directly induces calcification and SMAD1/5-signaling pathways in vascular smooth muscle cells.