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. 2022 May 17;9:872288. doi: 10.3389/fcvm.2022.872288

FIGURE 2.

FIGURE 2

The endothelial to mesenchymal transition (EndoMT) and phenotypic trans-differentiation from quiescent valve interstitial cells (qVICs) to activated valve interstitial cells (aVICs) in the progression of MMVD. The diagram illustrates the phenotypic, gene expression changes and cellular functional changes occurring during MMVD. The phenotypic conversion of endothelial cells into qVICs includes increased production of N-cadherin, vimentin and fibroblast-specific protein-1 (FSP-1). These events are accompanied by downregulation of the markers of endothelial cells such as CD31/platelet-endothelial cell adhesion molecule-1 (CD31/PECAM-1), vascular-endothelial cadherin (VE-cadherin), COL4, vascular epidermal growth factor receptor (VEGFR), and von Willebrand factor (vWF). Furthermore, the TGF-β-activated VICs show a significant increase in unique markers including α-smooth muscle actin (α-SMA), SM22 and Smemb (embryonic smooth muscle myosin) as well as the secretory proteins regulating the ECM disorganization including MMPs/TIMPs, IL-1β, IL-11, and IL-33.