Exosomes in Cardiovascular Diseases by Junjie Xiao & Sanda Cretoiu

Author:Junjie Xiao & Sanda Cretoiu
Language: eng
Format: epub
Publisher: Springer Singapore, Singapore

10.3.1 Exosome Fusion in Vascular Calcification

Changes in cell phenotype, specifically the epithelial-to-mesenchymal transition, were previously linked to elevated exosome-like vesicle secretion, although specific mechanisms between these phenotypic changes and exosome production are unknown [34]. In order to counterbalance calcifying milieu, MVs secreted by VSMCs are physiologically loaded with calcification inhibitors, such an endogenously expressed matrix Gla protein (MGP) and circulating fetuin-A (α2-Heremens–Schmid glycoprotein) [35] in physiological conditions. Fetuin A is a glycoprotein secreted mainly by the liver. On contrary, in patients with exaggerated vascular calcification, circulating fetuin-A is reduced [36].

In parallel, investigators established a pivotal role of MGP, which is able to attenuate vascular calcification in murine models of vascular calcification and diabetes (db/db) and in human islet amyloid polypeptide transgenic (HIP) rats, by specifically inhibiting BMP-2 signaling [37]. However, a prolonged mineral imbalance and/or inflammation induces reduction of MGP and fetuin-A inside MVs and enrichment with a protein–lipid complex consisting of phosphatidylserine (PS) and Annexin A6, which converts MVs into a nest for calcification (Fig. 10.2) [35, 36, 38, 39].

Fig. 10.2Schematic representation of exosome and proteins related to calcification (Adapted from Shanahan CM et al.). PS phosphatidylserine, MMP2 matrix metallopeptidase 2, MGP matrix Gla protein, TNF-α tumor necrosis factor-α

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