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

Masashi Harada, Meizi Jiang, Kensuke Terai, Hiroyuki Ebinuma, Nobuyuki Hiruta, Wolfgang J Schneider, Nobuo Sugo, Takeki Nagao, Hideaki Bujo

Journal: Clinica chimica acta; international journal of clinical chemistry 2019;490():69-76

PMID: 30550937

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Department of Neurosurgery, Toho University Sakura Medical Center, Sakura, Japan.; Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura 285-8741, Japan.; Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura 285-8741, Japan; Department of Surgical Pathology, Toho University Sakura Medical Center, Sakura, Japan.; Sekisui Medical Co Ltd, Tsukuba Research Institute, Ryugasaki, Japan.; Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria.; Department of Neurosurgery, Toho University Omori Medical Center, Omori, Japan.; Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura 285-8741, Japan. Electronic address: [email protected].

DOI: 10.1016/j.cca.2018.12.005

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MeSH Terms: Aged, 80 and over, Carotid Stenosis, Cell Differentiation, Cell Movement, Female, Humans, LDL-Receptor Related Proteins, Male, Membrane Transport Proteins, Myocytes, Smooth Muscle, Plaque, Atherosclerotic