Moreover, even in non-syndromic MVP, a complex, multifactorial interplay of genetic alterations and external factors, as well as mechanical stress, contributes to the development of alterations typical of myxomatous MVP, including TGF-β1 pathway activation and impaired expression of adherence molecules (e.g., upregulation of cadherin-11, vimentin and β-catenin, and downregulation of N-cadherin), transcription factors, and MMPs (Figure 3) (6, 29). Here, VIM is linked to familial mitral valve prolapse.