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Review
. 2021 Sep 11;22(18):9829.
doi: 10.3390/ijms22189829.

Role of Glycosylation in Vascular Calcification

Ainun Nizar Masbuchin  1   2 , Mohammad Saifur Rohman  2 , Ping-Yen Liu  1   3
Affiliations
Review

Role of Glycosylation in Vascular Calcification

Ainun Nizar Masbuchin et al. Int J Mol Sci. .

Abstract

Glycosylation is an important step in post-translational protein modification. Altered glycosylation results in an abnormality that causes diseases such as malignancy and cardiovascular diseases. Recent emerging evidence highlights the importance of glycosylation in vascular calcification. Two major types of glycosylation, N-glycosylation and O-glycosylation, are involved in vascular calcification. Other glycosylation mechanisms, which polymerize the glycosaminoglycan (GAG) chain onto protein, resulting in proteoglycan (PG), also have an impact on vascular calcification. This paper discusses the role of glycosylation in vascular calcification.

Keywords: N-glycosylation; O-glycosylation; medial calcification; proteoglycan; vascular calcification.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Proposed mechanism of how glycosylation of regulatory factors affects vascular calcification. Mechanism of vascular calcification involves loss of inhibitor and gain inducer. In the condition rich of phosphate and calcium, the VSMC transdifferentiates into osteoblast-like cell (top panel). Calcification inducers such as BMP2, FGF23, and ALP were recently reported to be modified by glycosylation. Even the master regulator of calcification, RUNX2, is also reported to be modified by glycosylation. The activation of an osteogenic program by RUNX2 subsequently induces formation and secretion of MVs. Secreted MVs contain enzymes that support calcification (e.g., ALP, (tissue nonspecific alkaline phosphatase (TNAP), which are potent calcification inducers). MVs serve as nidus for hydroxyapatite formation. Matrix vesicle formation is interfered by autophagy. Autophagy is considered to decrease vascular calcification. BMP2 increases calcification through inhibition of autophagy. BMP2 secretion is modified by glycosylation. Fully glycosylated proteoglycan induces VC via a BMP2-BMP2R-smad1/5/8 pathway. TGFβ-TGFβR induces calcification through smad2/3-β-catenin. This pathway inhibits autophagy, which eventually increases calcification. FGF23 secretion requires glycosylation by GALNT3. FGF23-klotho binding in VSMC activates an osteogenic program through ERK1/2. Overall, the increasing glycosylation will stabilize calcification inducers and eventually induce vascular calcification (middle and bottom panel). This figure is compiled from references [26,39,77,79,80,83,85,91,93,95,108,110,128,129,130,131]. The illustration was Created with BioRender.com.
See this image and copyright information in PMC

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