TY - JOUR
T1 - Aortic calcified particles modulate valvular endothelial and interstitial cells
AU - van Engeland, N.C.A.
AU - Bertazzo, S.
AU - Sarathchandra, P.
AU - McCormack, A.
AU - Bouten, C.V.C.
AU - Yacoub, M.H.
AU - Chester, A.H.
AU - Latif, N.
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/3/21
Y1 - 2017/3/21
N2 - 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.
AB - 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.
KW - Calcified particles
KW - Endothelial-to-mesenchymal transformation
KW - Osteogenesis
KW - Valve endothelial cells
KW - Valve interstitial cells
UR - http://www.scopus.com/inward/record.url?scp=85015666274&partnerID=8YFLogxK
U2 - 10.1016/j.carpath.2017.02.006
DO - 10.1016/j.carpath.2017.02.006
M3 - Article
C2 - 28319833
SN - 1054-8807
VL - 28
SP - 36
EP - 45
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
ER -