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Calciprotein particle-activated endothelial cells aggravate smooth muscle cell calcification via paracrine signalling.

作者信息

Feenstra Lian, Zeper Lara W, van de Langenberg Brenda, Kahlman Eveline J E M, de La Roij Guido, Reijrink Melanie, Bernay Benoit, Chatre Laurent, Kuipers Jeroen, Giepmans Ben N G, Mastik Mirjam F, Kooistra Wierd, Lodewijk Monique E, Zuidscherwoude Malou, Pol Robert A, Smith Edward R, Krenning Guido, de Baaij Jeroen H F, Hillebrands Jan-Luuk, Hoenderop Joost G J

机构信息

Department of Pathology and Medical Biology (HPC: EA10), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Department of Medical Biosciences, Radboud University Medical Center, P.O. Box 9101, 6500HB, Nijmegen, The Netherlands.

出版信息

Cell Mol Life Sci. 2025 Apr 26;82(1):177. doi: 10.1007/s00018-025-05702-z.


DOI:10.1007/s00018-025-05702-z
PMID:40287595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12033162/
Abstract

BACKGROUND: Vascular calcification is highly prevalent in Chronic Kidney Disease (CKD) and is associated with markedly increased cardiovascular risk. High serum phosphate in CKD increases calcification propensity via generation of circulating calciprotein particles (CPP2), crystalline nanoaggregates composed of calcium, phosphate, and serum proteins. CPP2 induce vascular calcification in vascular smooth muscle cells (VSMCs) in vitro. In vivo, endothelial cells, rather than VSMCs are primarily exposed to CPP2, yet understanding the influence of endothelial cells on vascular calcification is limited. METHODS: We investigated calcification-promoting signalling by endothelial cells on VSMCs. Effects of CPP2 exposure to endothelial cells on CPP2 uptake, endothelial cell activation, and endothelial cell-derived secretome were studied. Effects of the secretome on VSMC calcification were investigated. Using NanoString nCounter analysis the effects of CPP2-activated endothelial cell-conditioned medium on VSMCs gene expression were mapped. RESULTS: Endothelial cells internalise CPP2 and elevate ICAM-1, E-selectin, and VCAM-1-mRNA expression, indicating endothelial activation. VSMCs cultured in conditioned medium from CPP2-activated endothelial cells demonstrated enhanced calcification, suggesting that CPP2-activated endothelial cells release pro-calcifying soluble factors. Mass spectrometry was utilized to identify 1171 proteins in the CPP2-activated endothelial cells' secretome. Among these, 76 proteins were differentially expressed compared to control endothelial cells' secretome, including proteins related to blood vessel development, extracellular matrix remodelling, and oxidative stress-related processes. Finally, endothelial cell-derived paracrine factors present in conditioned medium enhanced mRNA-expression of calcification-related factors in VSMCs. CONCLUSIONS: CPP2-activated endothelial cells promote VSMC calcification via paracrine signalling. In response to these paracrine factors, VSMCs increase the expression of pro-calcification genes.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/13d52db020eb/18_2025_5702_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/31c82bab722c/18_2025_5702_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/6a45d9621453/18_2025_5702_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/ca5b9cd5354a/18_2025_5702_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/dd53a3676fdd/18_2025_5702_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/49f90d244675/18_2025_5702_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/13d52db020eb/18_2025_5702_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/31c82bab722c/18_2025_5702_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/6a45d9621453/18_2025_5702_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/ca5b9cd5354a/18_2025_5702_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/dd53a3676fdd/18_2025_5702_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/49f90d244675/18_2025_5702_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aa2/12033162/13d52db020eb/18_2025_5702_Fig6_HTML.jpg

相似文献

[1]
Calciprotein particle-activated endothelial cells aggravate smooth muscle cell calcification via paracrine signalling.

Cell Mol Life Sci. 2025-4-26

[2]
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[3]
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[4]
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[5]
Liver and spleen predominantly mediate calciprotein particle clearance in a rat model of chronic kidney disease.

Am J Physiol Renal Physiol. 2024-4-1

[6]
Matrix vesicles induce calcification of recipient vascular smooth muscle cells through multiple signaling pathways.

Kidney Int. 2017-10-9

[7]
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[8]
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Pflugers Arch. 2021-12

[9]
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[10]
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本文引用的文献

[1]
Proteomic Profiling of Endothelial Cell Secretomes After Exposure to Calciprotein Particles Reveals Downregulation of Basement Membrane Assembly and Increased Release of Soluble CD59.

Int J Mol Sci. 2024-10-23

[2]
Calciprotein particle counts associate with vascular remodelling in chronic kidney disease.

Cardiovasc Res. 2024-12-4

[3]
Redox Metabolism and Vascular Calcification in Chronic Kidney Disease.

Biomolecules. 2023-9-20

[4]
Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33.

Biomolecules. 2023-7-7

[5]
Atherosclerosis Calcification: Focus on Lipoproteins.

Metabolites. 2023-3-21

[6]
Calciprotein Particles Induce Endothelial Dysfunction by Impairing Endothelial Nitric Oxide Metabolism.

Arterioscler Thromb Vasc Biol. 2023-3

[7]
Calciprotein Particles Cause Physiologically Significant Pro-Inflammatory Response in Endothelial Cells and Systemic Circulation.

Int J Mol Sci. 2022-11-29

[8]
Exosomal STAT1 derived from high phosphorus‑stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/β‑catenin signaling pathway.

Int J Mol Med. 2022-12

[9]
Effect of the phosphate binder sucroferric oxyhydroxide in dialysis patients on endogenous calciprotein particles, inflammation, and vascular cells.

Nephrol Dial Transplant. 2023-5-4

[10]
The crosstalk between endothelial cells and vascular smooth muscle cells aggravates high phosphorus-induced arterial calcification.

Cell Death Dis. 2022-7-26

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