Elastin Structure, Synthesis, Regulatory Mechanism and Relationship With Cardiovascular Diseases

Figures

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  FIGURE 1. Human tropoelastin domain structure. Tropoelastin contains alternating hydrophobic (white rectangle) and hydrophilic cross-linking domains (black rectangle), and the width of the rectangles corresponds to the length of the domains. The number above the domains represents the sequence of exons that encode them. Among exons, exon 36 encodes a hydrophilic C-terminus (red rectangle) in addition to a 3′-untranslated region (blue rectangle).

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  FIGURE 2. Tropoelastin secretory/assembly pathway. The synthesis of tropoelastin begins with the transcription of the ELN gene in the nucleus. In the endoplasmic reticulum, tropoelastin interacts with EBP and folds in structure. After the storage and transport of Golgi, the complex of EBP and tropoelastin is secreted to the cell surface for self-assembly. Then, tropoelastin dissociates from EBP and deposits onto the microfibril scaffold. In the presence of LOX, tropoelastin cross-links and eventually forms mature elastic fibers.

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  FIGURE 3. Elastin synthesis molecular regulatory networks. Elastin synthesis is dynamically regulated by a variety of molecules. Activated MMP may promote the degradation of elastin and its precursor tropoelastin, while the increase of TIMP may stabilize the synthesis of elastin. TNF-α, IL-1β, and HB-EGF may stimulate MMP activation and inhibit TIMP to induce elastin degradation. However, TGFβ1 may inhibit MMP activation and stimulate TIMP expression to suppress elastin degradation. Additionally, miR-29b, miR-195, and miR-181b are epigenetic regulatory molecules of elastin. These miRNAs may inhibit elastin expression by targeting the 3′ UTR of ELN mRNA, and restrained MMP and TIMP activity to involve in the regulation of elastin synthesis.