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Calcification in Werner syndrome associated with lymphatic vessels aging
Hideyuki Ogata1, Shinsuke Akita1, Sanae Ikehara2,3
1Department of Plastic, Reconstructive, and Aesthetic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Aging
|December 27, 2021
Summary
Werner syndrome (WS) involves premature aging, skin ulcers, and calcification. This study links WS calcification to lymphatic vessel remodeling and WRN protein accumulation, suggesting impaired lymphatic drainage.
Area of Science:
- Vascular Biology
- Dermatology
- Genetics
Background:
- Werner syndrome (WS) is a hereditary premature aging disease.
- Key WS symptoms include subcutaneous calcification, pain, and chronic skin ulcers.
- The mechanism behind WS-related calcification is not fully understood.
Purpose of the Study:
- To investigate the mechanism of subcutaneous calcification in Werner syndrome.
- To analyze lymphatic vessel morphology and WRN protein distribution in WS skin ulcers.
- To explore the relationship between lymphatic remodeling, WRN protein accumulation, and calcification in WS.
Main Methods:
- Histological analysis of skin from WS patients with calcification.
- Morphological comparison of lymphatic vessels in WS and peripheral artery disease (PAD) patients.
- Fluorescence immunohistochemical analysis for WRN protein localization.
Main Results:
- Calcium phosphate accumulation was observed in the lymphatic vessels of WS skin ulcers.
- WS lymphatic vessels showed remodeling: narrower lumen (LA) and increased microvessel density (MLVD).
- WRN proteins accumulated in the cytoplasm of endothelial cells within remodeled lymphatic vessels.
Conclusions:
- Lymphatic vessel calcification in WS is associated with lymphatic remodeling.
- Accumulation of WRN mutant proteins in endothelial cells may indicate impaired lymphatic drainage.
- WRN protein accumulation is a potential indicator of increased risk for skin ulcers and calcification in WS.
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