van Engeland, NCA;
Bertazzo, S;
Sarathchandra, P;
McCormack, A;
Bouten, CVC;
Yacoub, MH;
Chester, AH;
(2017)
Aortic calcified particles modulate valvular endothelial and interstitial cells.
Cardiovascular Pathology
, 28
pp. 36-45.
10.1016/j.carpath.2017.02.006.
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Abstract
Background: Normal and calcified human valve cusps, coronary arteries, and aortae harbor spherical calcium phosphate microparticles of identical composition and crystallinity, and their role remains unknown. Objective: The objective was to examine the direct effects of isolated calcified particles on human valvular cells. Method and results: Calcified particles were isolated from healthy and diseased aortae, characterized, quantitated, and applied to valvular endothelial cells (VECs) and interstitial cells (VICs). Cell differentiation, viability, and proliferation were analyzed. Particles were heterogeneous, differing in size and shape, and were crystallized as calcium phosphate. Diseased donors had significantly more calcified particles compared to healthy donors (P<.05), but there were no differences between the composition of the particles from healthy and diseased donors. VECs treated with calcified particles showed a significant decrease in CD31 and VE-cadherin and an increase in von Willebrand factor expression, P<.05. There were significantly increased α-SMA and osteopontin in treated VICs (P<.05), significantly decreased VEC and VIC viability (P<.05), and significantly increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive VECs (P<.05) indicating apoptosis when treated with the calcified particles. Conclusions: Isolated calcified particles from human aortae are not innocent bystanders but induce a phenotypical and pathological change of VECs and VICs characteristic of activated and pathological cells. Therapy tailored to reduce these calcified particles should be investigated.
| Type: | Article |
|---|---|
| Title: | Aortic calcified particles modulate valvular endothelial and interstitial cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.carpath.2017.02.006 |
| Publisher version: | http://doi.org/10.1016/j.carpath.2017.02.006 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Calcified particles, Valve endothelial cells, Valve interstitial cells, Osteogenesis, Endothelial-to-mesenchymal transformation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1551739 |
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