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Valvular interstitial cells suppress calcification of valvular endothelial cells. / Hjortnaes, Jesper; Shapero, Kayle; Goettsch, Claudia; Hutcheson, Joshua D.; Keegan, Joshua; Kluin, Jolanda; Mayer, John E.; Bischoff, Joyce; Aikawa, Elena.

In: Atherosclerosis, Vol. 242, No. 1, 2015, p. 251-260.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Hjortnaes, J, Shapero, K, Goettsch, C, Hutcheson, JD, Keegan, J, Kluin, J, Mayer, JE, Bischoff, J & Aikawa, E 2015, 'Valvular interstitial cells suppress calcification of valvular endothelial cells', Atherosclerosis, vol. 242, no. 1, pp. 251-260. https://doi.org/10.1016/j.atherosclerosis.2015.07.008

APA

Hjortnaes, J., Shapero, K., Goettsch, C., Hutcheson, J. D., Keegan, J., Kluin, J., Mayer, J. E., Bischoff, J., & Aikawa, E. (2015). Valvular interstitial cells suppress calcification of valvular endothelial cells. Atherosclerosis, 242(1), 251-260. https://doi.org/10.1016/j.atherosclerosis.2015.07.008

Vancouver

Hjortnaes J, Shapero K, Goettsch C, Hutcheson JD, Keegan J, Kluin J et al. Valvular interstitial cells suppress calcification of valvular endothelial cells. Atherosclerosis. 2015;242(1):251-260. https://doi.org/10.1016/j.atherosclerosis.2015.07.008

Author

Hjortnaes, Jesper ; Shapero, Kayle ; Goettsch, Claudia ; Hutcheson, Joshua D. ; Keegan, Joshua ; Kluin, Jolanda ; Mayer, John E. ; Bischoff, Joyce ; Aikawa, Elena. / Valvular interstitial cells suppress calcification of valvular endothelial cells. In: Atherosclerosis. 2015 ; Vol. 242, No. 1. pp. 251-260.

BibTeX

@article{9694d8aa3625491ca4a893d174ccb5c2,
title = "Valvular interstitial cells suppress calcification of valvular endothelial cells",
abstract = "Background: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Approach and results: VEC clones underwent TGF-beta(1)-mediated EndMT, shown by significantly increased mRNA expression of the EndMT markers alpha-SMA (5.3 +/- 1.2), MMP-2 (13.5 +/- 0.6) and Slug (12 +/- 2.1) (p <0.05), (compared to unstimulated controls). To study the effects of VIC on VEC EndMT, clonal populations of VICs were derived from the same valve leaflets, placed in co-culture with VECs, and grown in control/TGF-beta(1) supplemented media. In the presence of VICs, EndMT was inhibited, shown by decreased mRNA expression of alpha-SMA (0.1 +/- 0.5), MMP-2 (0.1 +/- 0.1), and Slug (0.2 +/- 0.2) (p <0.05). When cultured in osteogenic media, VECs demonstrated osteogenic changes confirmed by increase in mRNA expression of osteocalcin (8.6 +/- 1.3), osteopontin (3.7 +/- 0.3), and Runx2 (5.5 +/- 1.5). The VIC presence inhibited VEC osteogenesis, demonstrated by decreased expression of osteocalcin (0.4 +/- 0.1) and osteopontin (0.2 +/- 0.1) (p <0.05). Time course analysis suggested that EndMT precedes osteogenesis, shown by an initial increase of alpha-SMA and MMP-2 (day 7), followed by an increase of osteopontin and osteocalcin (day 14). Conclusions: The data indicate that EndMT may precede VEC osteogenesis. This study shows that VICs inhibit VEC EndMT and osteogenesis, indicating the importance of VEC-VIC interactions in valve homeostasis. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NCND license",
author = "Jesper Hjortnaes and Kayle Shapero and Claudia Goettsch and Hutcheson, {Joshua D.} and Joshua Keegan and Jolanda Kluin and Mayer, {John E.} and Joyce Bischoff and Elena Aikawa",
year = "2015",
doi = "10.1016/j.atherosclerosis.2015.07.008",
language = "English",
volume = "242",
pages = "251--260",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - Valvular interstitial cells suppress calcification of valvular endothelial cells

AU - Hjortnaes, Jesper

AU - Shapero, Kayle

AU - Goettsch, Claudia

AU - Hutcheson, Joshua D.

AU - Keegan, Joshua

AU - Kluin, Jolanda

AU - Mayer, John E.

AU - Bischoff, Joyce

AU - Aikawa, Elena

PY - 2015

Y1 - 2015

N2 - Background: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Approach and results: VEC clones underwent TGF-beta(1)-mediated EndMT, shown by significantly increased mRNA expression of the EndMT markers alpha-SMA (5.3 +/- 1.2), MMP-2 (13.5 +/- 0.6) and Slug (12 +/- 2.1) (p <0.05), (compared to unstimulated controls). To study the effects of VIC on VEC EndMT, clonal populations of VICs were derived from the same valve leaflets, placed in co-culture with VECs, and grown in control/TGF-beta(1) supplemented media. In the presence of VICs, EndMT was inhibited, shown by decreased mRNA expression of alpha-SMA (0.1 +/- 0.5), MMP-2 (0.1 +/- 0.1), and Slug (0.2 +/- 0.2) (p <0.05). When cultured in osteogenic media, VECs demonstrated osteogenic changes confirmed by increase in mRNA expression of osteocalcin (8.6 +/- 1.3), osteopontin (3.7 +/- 0.3), and Runx2 (5.5 +/- 1.5). The VIC presence inhibited VEC osteogenesis, demonstrated by decreased expression of osteocalcin (0.4 +/- 0.1) and osteopontin (0.2 +/- 0.1) (p <0.05). Time course analysis suggested that EndMT precedes osteogenesis, shown by an initial increase of alpha-SMA and MMP-2 (day 7), followed by an increase of osteopontin and osteocalcin (day 14). Conclusions: The data indicate that EndMT may precede VEC osteogenesis. This study shows that VICs inhibit VEC EndMT and osteogenesis, indicating the importance of VEC-VIC interactions in valve homeostasis. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NCND license

AB - Background: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Approach and results: VEC clones underwent TGF-beta(1)-mediated EndMT, shown by significantly increased mRNA expression of the EndMT markers alpha-SMA (5.3 +/- 1.2), MMP-2 (13.5 +/- 0.6) and Slug (12 +/- 2.1) (p <0.05), (compared to unstimulated controls). To study the effects of VIC on VEC EndMT, clonal populations of VICs were derived from the same valve leaflets, placed in co-culture with VECs, and grown in control/TGF-beta(1) supplemented media. In the presence of VICs, EndMT was inhibited, shown by decreased mRNA expression of alpha-SMA (0.1 +/- 0.5), MMP-2 (0.1 +/- 0.1), and Slug (0.2 +/- 0.2) (p <0.05). When cultured in osteogenic media, VECs demonstrated osteogenic changes confirmed by increase in mRNA expression of osteocalcin (8.6 +/- 1.3), osteopontin (3.7 +/- 0.3), and Runx2 (5.5 +/- 1.5). The VIC presence inhibited VEC osteogenesis, demonstrated by decreased expression of osteocalcin (0.4 +/- 0.1) and osteopontin (0.2 +/- 0.1) (p <0.05). Time course analysis suggested that EndMT precedes osteogenesis, shown by an initial increase of alpha-SMA and MMP-2 (day 7), followed by an increase of osteopontin and osteocalcin (day 14). Conclusions: The data indicate that EndMT may precede VEC osteogenesis. This study shows that VICs inhibit VEC EndMT and osteogenesis, indicating the importance of VEC-VIC interactions in valve homeostasis. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NCND license

U2 - 10.1016/j.atherosclerosis.2015.07.008

DO - 10.1016/j.atherosclerosis.2015.07.008

M3 - Article

C2 - 26232165

VL - 242

SP - 251

EP - 260

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -

ID: 2826551