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Citations to this article

Sortilin mediates vascular calcification via its recruitment into extracellular vesicles
Claudia Goettsch, … , Sasha A. Singh, Elena Aikawa
Claudia Goettsch, … , Sasha A. Singh, Elena Aikawa
Published March 7, 2016
Citation Information: J Clin Invest. 2016;126(4):1323-1336. https://doi.org/10.1172/JCI80851.
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Research Article Vascular biology Article has an altmetric score of 13

Sortilin mediates vascular calcification via its recruitment into extracellular vesicles

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Abstract

Vascular calcification is a common feature of major cardiovascular diseases. Extracellular vesicles participate in the formation of microcalcifications that are implicated in atherosclerotic plaque rupture; however, the mechanisms that regulate formation of calcifying extracellular vesicles remain obscure. Here, we have demonstrated that sortilin is a key regulator of smooth muscle cell (SMC) calcification via its recruitment to extracellular vesicles. Sortilin localized to calcifying vessels in human and mouse atheromata and participated in formation of microcalcifications in SMC culture. Sortilin regulated the loading of the calcification protein tissue nonspecific alkaline phosphatase (TNAP) into extracellular vesicles, thereby conferring its calcification potential. Furthermore, SMC calcification required Rab11-dependent trafficking and FAM20C/casein kinase 2–dependent C-terminal phosphorylation of sortilin. In a murine model, Sort1-deficiency reduced arterial calcification but did not affect bone mineralization. Additionally, transfer of sortilin-deficient BM cells to irradiated atherosclerotic mice did not affect vascular calcification, indicating a primary role of SMC-derived sortilin. Together, the results of this study identify sortilin phosphorylation as a potential therapeutic target for ectopic calcification/microcalcification and may clarify the mechanism that underlies the genetic association between the SORT1 gene locus and coronary artery calcification.

Authors

Claudia Goettsch, Joshua D. Hutcheson, Masanori Aikawa, Hiroshi Iwata, Tan Pham, Anders Nykjaer, Mads Kjolby, Maximillian Rogers, Thomas Michel, Manabu Shibasaki, Sumihiko Hagita, Rafael Kramann, Daniel J. Rader, Peter Libby, Sasha A. Singh, Elena Aikawa

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 Total
Citations: 2 10 16 28 15 19 8 12 16 4 130
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (4)

Title and authors Publication Year
Imaging Atherosclerotic Plaque Calcification: Translating Biology
G Bailey, J Meadows, AR Morrison
Current Atherosclerosis Reports 2016
A single injection of gain-of-function mutant PCSK9 adeno-associated virus vector induces cardiovascular calcification in mice with no genetic modification
C Goettsch, JD Hutcheson, S Hagita, MA Rogers, MD Creager, T Pham, J Choi, AK Mlynarchik, B Pieper, M Kjolby, M Aikawa, E Aikawa
Atherosclerosis 2016
Calcification in atherosclerotic lesions:
H Lu, M Sheppard, A Daugherty
Current Opinion in Lipidology 2016
Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β ProductionHighlights
N Ceneri, L Zhao, BD Young, A Healy, S Coskun, H Vasavada, TO Yarovinsky, K Ike, R Pardi, L Qin, L Qin, G Tellides, K Hirschi, J Meadows, R Soufer, HJ Chun, MM Sadeghi, JR Bender, AR Morrison
Arteriosclerosis, thrombosis, and vascular biology 2016

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