Aortic calcified particles modulate valvular endothelial and interstitial cells.
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.


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.
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK; Eindhoven University of Technology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, 5600 MB Eindhoven, the Netherlands.
Nicole C A
NCA
van Engeland
University College London, Department of Medical Physics & Biomedical Engineering, Malet Place Engineering Building, London, WC1E 6BT, UK.
Sergio
S
Bertazzo
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Padmini
P
Sarathchandra
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Ann
A
McCormack
Eindhoven University of Technology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, 5600 MB Eindhoven, the Netherlands.
Carlijn V C
CVC
Bouten
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Magdi H
MH
Yacoub
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Adrian H
AH
Chester
Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK. Electronic address: n.latif@imperial.ac.uk.
Najma
N
Latif
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D001018:Aortic Diseases / Q000378:metabolism* / Q000473:pathology; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006349:Heart Valve Diseases / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism; D010316:Particle Size; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013997:Time Factors; D061205:Vascular Calcification / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism; D000099152:Cadherin 5
D000199:Actins; D015703:Antigens, CD; D015820:Cadherins; D002118:Calcium; D053495:Osteopontin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D000099152:Cadherin 5; C541116:ACTA2 protein, human; C506895:SPP1 protein, human
Calcified particles; Endothelial-to-mesenchymal transformation; Osteogenesis; Valve endothelial cells; Valve interstitial cells