Levels of circulating soluble LR11, a regulator of smooth muscle cell migration, are highly associated with atherosclerotic plaques in patients with carotid artery stenosis

Background: The levels of plasma sLR11, released from intimal SMCs, are positively associated with intima-media thickness (IMT) in asymptomatic subjects. We have evaluated the yet unknown pathological significance of sLR11 for plaque conditions in patients with carotid artery stenosis. Methods: The presence of LR11 in carotid plaques was investigated using autopsy specimens. A clinical ultrasonography study for elucidating relationships between sLR11 and plaque condition was performed in 46 patients. Results: Immunohistochemistry showed high levels of LR11 in SMCs within thickened intima and at the media-intima border of atherosclerotic carotid plaques. The levels of sLR11 in patients were clearly elevated compared to healthy controls. Univariate analysis of sLR11 revealed significant positive correlation with plaque score and a tendency to correlate with the stenotic fraction. Univariate and multiple regression analyses of plaque scores showed that sLR11, maximum IMT, and HDL-cholesterol independently determined plaque score. Finally, univariate analysis of initial sLR11 levels for changes in imaging markers after one-year follow-up showed that initial sLR11 levels significantly correlated with stenotic fraction progression. Conclusions: The levels of sLR11, abundantly expressed in carotid atherosclerotic plaques, are highly associated with increased plaque score. sLR11 levels may be predictive of plaque conditions in patients with advanced carotid atherosclerosis.