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01-04-2019 | Original Article

RAGE/galectin-3 yields intraplaque calcification transformation via sortilin

Authors: Zhen Sun, Zhongqun Wang, Lihua Li, Jinchuan Yan, Chen Shao, Zhengyang Bao, Lele Jing, Qiwen Pang, Yue Geng, Lili Zhang

Published in: Acta Diabetologica | Issue 4/2019

Abstract

Aims

Macrocalcification and microcalcification present different clinical risks, but the regulatory of their formation was unclear. Therefore, this study explored the underlying mechanisms of macrocalcification and microcalcification in diabetes mellitus.

Methods

Anterior tibial arteries of amputated diabetic feet were collected. According to the calcium content, patients were divided into less-calcification group and more-calcification group. And calcification morphology in plaques was observed. For further study, an in vivo mouse diabetic atherosclerosis model and an in vitro primary mouse aortic smooth muscle cell model were established. After the receptors for AGEs (RAGE) or galectin-3 were silenced, calcified nodule sizes and sortilin expression were determined. Scanning electron microscopy (SEM) was performed to detect the aggregation of matrix vesicles with the inhibition or promotion of sortilin.

Results

Both macro- and microcalcification were found in human anterior tibial artery plaques. Macrocalcification formed after the silencing of RAGE, and microcalcification formed after the silencing of galectin-3. In the process of RAGE- or galcetin-3-induced calcification, sortilin played an important role downstream. SEM showed that sortilin promoted the aggregation of MVs in the early stage of calcification and formed larger calcified nodules.

Conclusion

RAGE downregulated sortilin and then transmitted microcalcification signals, whereas galectin-3 upregulated sortilin, which accelerated the aggregation of MVs in the early stage of calcification and mediated the formation of macrocalcifications, These data illustrate the progression of two calcification types and suggest sortilin as a potential target for early intervention of calcification and as an effective biomarker for the assessment of long-term clinical risk and prognosis.

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Title: RAGE/galectin-3 yields intraplaque calcification transformation via sortilin
Authors: Zhen Sun
Zhongqun Wang
Lihua Li
Jinchuan Yan
Chen Shao
Zhengyang Bao
Lele Jing
Qiwen Pang
Yue Geng
Lili Zhang
Publication date: 01-04-2019
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 4/2019
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-1273-1

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