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Open AccessArticle

Calciprotein Particles Cause Endothelial Dysfunction under Flow

Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, 6 Sosnovy Boulevard, 650002 Kemerovo, Russia
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8802; https://doi.org/10.3390/ijms21228802
Received: 18 October 2020 / Revised: 11 November 2020 / Accepted: 19 November 2020 / Published: 20 November 2020
(This article belongs to the Special Issue Molecular Research on Arteriosclerosis and Thrombosis)
Calciprotein particles (CPPs), which increasingly arise in the circulation during the disorders of mineral homeostasis, represent a double-edged sword protecting the human organism from extraskeletal calcification but potentially causing endothelial dysfunction. Existing models, however, failed to demonstrate the detrimental action of CPPs on endothelial cells (ECs) under flow. Here, we applied a flow culture system, where human arterial ECs were co-incubated with CPPs for 4 h, and a normolipidemic and normotensive rat model (10 daily intravenous injections of CPPs) to simulate the scenario occurring in vivo in the absence of confounding cardiovascular risk factors. Pathogenic effects of CPPs were investigated by RT-qPCR and Western blotting profiling of the endothelial lysate. CPPs were internalised within 1 h of circulation, inducing adhesion of peripheral blood mononuclear cells to ECs. Molecular profiling revealed that CPPs stimulated the expression of pro-inflammatory cell adhesion molecules VCAM1 and ICAM1 and upregulated transcription factors of endothelial-to-mesenchymal transition (Snail, Slug and Twist1). Furthermore, exposure to CPPs reduced the production of atheroprotective transcription factors KLF2 and KLF4 and led to YAP1 hypophosphorylation, potentially disturbing the mechanisms responsible for the proper endothelial mechanotransduction. Taken together, our results suggest the ability of CPPs to initiate endothelial dysfunction at physiological flow conditions. View Full-Text
Keywords: calciprotein particles; endothelial cells; endothelial dysfunction; shear stress; laminar flow; turbulent flow; monocyte adhesion; cell adhesion molecules; endothelial-to-mesenchymal transition; mechanotransduction calciprotein particles; endothelial cells; endothelial dysfunction; shear stress; laminar flow; turbulent flow; monocyte adhesion; cell adhesion molecules; endothelial-to-mesenchymal transition; mechanotransduction
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MDPI and ACS Style

Shishkova, D.; Markova, V.; Sinitsky, M.; Tsepokina, A.; Velikanova, E.; Bogdanov, L.; Glushkova, T.; Kutikhin, A. Calciprotein Particles Cause Endothelial Dysfunction under Flow. Int. J. Mol. Sci. 2020, 21, 8802. https://doi.org/10.3390/ijms21228802

AMA Style

Shishkova D, Markova V, Sinitsky M, Tsepokina A, Velikanova E, Bogdanov L, Glushkova T, Kutikhin A. Calciprotein Particles Cause Endothelial Dysfunction under Flow. International Journal of Molecular Sciences. 2020; 21(22):8802. https://doi.org/10.3390/ijms21228802

Chicago/Turabian Style

Shishkova, Daria; Markova, Victoria; Sinitsky, Maxim; Tsepokina, Anna; Velikanova, Elena; Bogdanov, Leo; Glushkova, Tatiana; Kutikhin, Anton. 2020. "Calciprotein Particles Cause Endothelial Dysfunction under Flow" Int. J. Mol. Sci. 21, no. 22: 8802. https://doi.org/10.3390/ijms21228802

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