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Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells

Parathyroid hormone (PTH) is a key regulator of calcium, phosphate and vitamin D metabolism. Although it has been reported that aortic valve calcification was positively associated with PTH, the pathophysiological mechanisms and the direct effects of PTH on human valvular cells remain unclear. Here...

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Autores principales: Vadana, Mihaela, Cecoltan, Sergiu, Ciortan, Letitia, Macarie, Razvan D., Mihaila, Andreea C., Tucureanu, Monica M., Gan, Ana-Maria, Simionescu, Maya, Manduteanu, Ileana, Droc, Ionel, Butoi, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998852/
https://www.ncbi.nlm.nih.gov/pubmed/35409134
http://dx.doi.org/10.3390/ijms23073776
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author Vadana, Mihaela
Cecoltan, Sergiu
Ciortan, Letitia
Macarie, Razvan D.
Mihaila, Andreea C.
Tucureanu, Monica M.
Gan, Ana-Maria
Simionescu, Maya
Manduteanu, Ileana
Droc, Ionel
Butoi, Elena
author_facet Vadana, Mihaela
Cecoltan, Sergiu
Ciortan, Letitia
Macarie, Razvan D.
Mihaila, Andreea C.
Tucureanu, Monica M.
Gan, Ana-Maria
Simionescu, Maya
Manduteanu, Ileana
Droc, Ionel
Butoi, Elena
author_sort Vadana, Mihaela
collection PubMed
description Parathyroid hormone (PTH) is a key regulator of calcium, phosphate and vitamin D metabolism. Although it has been reported that aortic valve calcification was positively associated with PTH, the pathophysiological mechanisms and the direct effects of PTH on human valvular cells remain unclear. Here we investigated if PTH induces human valvular endothelial cells (VEC) dysfunction that in turn could impact the switch of valvular interstitial cells (VIC) to an osteoblastic phenotype. Human VEC exposed to PTH were analyzed by qPCR, western blot, Seahorse, ELISA and immunofluorescence. Our results showed that exposure of VEC to PTH affects VEC metabolism and functions, modifications that were accompanied by the activation of p38MAPK and ERK1/2 signaling pathways and by an increased expression of osteogenic molecules (BMP-2, BSP, osteocalcin and Runx2). The impact of dysfunctional VEC on VIC was investigated by exposure of VIC to VEC secretome, and the results showed that VIC upregulate molecules associated with osteogenesis (BMP-2/4, osteocalcin and TGF-β1) and downregulate collagen I and III. In summary, our data show that PTH induces VEC dysfunction, which further stimulates VIC to differentiate into a pro-osteogenic pathological phenotype related to the calcification process. These findings shed light on the mechanisms by which PTH participates in valve calcification pathology and suggests that PTH and the treatment of hyperparathyroidism represent a therapeutic strategy to reduce valvular calcification.
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spelling pubmed-89988522022-04-12 Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells Vadana, Mihaela Cecoltan, Sergiu Ciortan, Letitia Macarie, Razvan D. Mihaila, Andreea C. Tucureanu, Monica M. Gan, Ana-Maria Simionescu, Maya Manduteanu, Ileana Droc, Ionel Butoi, Elena Int J Mol Sci Article Parathyroid hormone (PTH) is a key regulator of calcium, phosphate and vitamin D metabolism. Although it has been reported that aortic valve calcification was positively associated with PTH, the pathophysiological mechanisms and the direct effects of PTH on human valvular cells remain unclear. Here we investigated if PTH induces human valvular endothelial cells (VEC) dysfunction that in turn could impact the switch of valvular interstitial cells (VIC) to an osteoblastic phenotype. Human VEC exposed to PTH were analyzed by qPCR, western blot, Seahorse, ELISA and immunofluorescence. Our results showed that exposure of VEC to PTH affects VEC metabolism and functions, modifications that were accompanied by the activation of p38MAPK and ERK1/2 signaling pathways and by an increased expression of osteogenic molecules (BMP-2, BSP, osteocalcin and Runx2). The impact of dysfunctional VEC on VIC was investigated by exposure of VIC to VEC secretome, and the results showed that VIC upregulate molecules associated with osteogenesis (BMP-2/4, osteocalcin and TGF-β1) and downregulate collagen I and III. In summary, our data show that PTH induces VEC dysfunction, which further stimulates VIC to differentiate into a pro-osteogenic pathological phenotype related to the calcification process. These findings shed light on the mechanisms by which PTH participates in valve calcification pathology and suggests that PTH and the treatment of hyperparathyroidism represent a therapeutic strategy to reduce valvular calcification. MDPI 2022-03-29 /pmc/articles/PMC8998852/ /pubmed/35409134 http://dx.doi.org/10.3390/ijms23073776 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vadana, Mihaela
Cecoltan, Sergiu
Ciortan, Letitia
Macarie, Razvan D.
Mihaila, Andreea C.
Tucureanu, Monica M.
Gan, Ana-Maria
Simionescu, Maya
Manduteanu, Ileana
Droc, Ionel
Butoi, Elena
Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title_full Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title_fullStr Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title_full_unstemmed Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title_short Parathyroid Hormone Induces Human Valvular Endothelial Cells Dysfunction That Impacts the Osteogenic Phenotype of Valvular Interstitial Cells
title_sort parathyroid hormone induces human valvular endothelial cells dysfunction that impacts the osteogenic phenotype of valvular interstitial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998852/
https://www.ncbi.nlm.nih.gov/pubmed/35409134
http://dx.doi.org/10.3390/ijms23073776
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