Key result
TGF-β1 significantly upregulated EndMT, while bFGF or VEGF markedly downregulated it, and collagen IV and fibronectin promoted the EndMT process in adult ovine mitral valve endothelial cells.
High-throughput cellular microarrays demonstrate that TGF-β1, collagen IV, and fibronectin promote endothelial-to-mesenchymal transformation in valvular endothelium, whereas bFGF and VEGF downregulate the process.
Should not yet change valve disease management; leaves open whether these factors modulate human mitral valve EndMT in vivo.
In the developing heart, a specific subset of endocardium undergoes an endothelial-to-mesenchymal transformation (EndMT) thus forming nascent valve leaflets. Extracellular matrix (ECM) proteins and growth factors (GFs) play important roles in regulating EndMT but the combinatorial effect of GFs with ECM proteins is less well understood. Here we use microscale engineering techniques to create single, binary, and tertiary component microenvironments to investigate the combinatorial effects of ECM proteins and GFs on the attachment and transformation of adult ovine mitral valve endothelial cells to a mesenchymal phenotype. With the combinatorial microenvironment microarrays, we utilized 60 different combinations of ECM proteins (Fibronectin, Collagen I, II, IV, Laminin) and GFs (TGF-β1, bFGF, VEGF) and were able to identify new microenvironmental conditions capable of modulating EndMT in MVECs. Experimental results indicated that TGF-β1 significantly upregulated the EndMT while either bFGF or VEGF downregulated EndMT process markedly. Also, ECM proteins could influence both the attachment of MVECs and the response of MVECs to GFs. In terms of attachment, fibronectin is significantly better for the adhesion of MVECs among the five tested proteins. Overall collagen IV and fibronectin appeared to play important roles in promoting EndMT process. Great consistency between macroscale and microarrayed experiments and present studies demonstrates that high-throughput cellular microarrays are a promising approach to study the regulation of EndMT in valvular endothelium. Biotechnol. Bioeng. 2016;113: 1403-1412.
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Wang et al. (2015) studied Endothelial-to-mesenchymal transformation (EndMT). Combinations of ECM proteins and growth factors was evaluated on Attachment and transformation to a mesenchymal phenotype (EndMT). TGF-β1 significantly upregulated EndMT, while bFGF or VEGF markedly downregulated it, and collagen IV and fibronectin promoted the EndMT process in adult ovine mitral valve endothelial cells.
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