Apelin Provides an Alternative Function to Estrogen in Regulating Lymphatic Vascular Integrity.

Lymphatic flow is decreased in postmenopausal women, and decreased lymphatic drainage tends to cause lymphedema [ [1] Vanneuville G. Mestas D. Le Bouedec G. Veyre A. Dauplat J. Escande G. et al. The lymphatic drainage of the human ovary in vivo investigated by isotopic lymphography before and after the menopause. Surg. Radiol. Anat. 1991; 13: 221-226 Crossref PubMed Scopus (18) Google Scholar ]. This can be prevented by administration of hormone replacement therapy (HRT) containing 17β-estradiol (E2), which induces the expression of lymphangiogenic genes, resulting in protection from lymphedema [ [2] Morfoisse F. Tatin F. Chaput B. Therville N. Vaysse C. Metivier R. et al. Lymphatic vasculature requires estrogen receptor-alpha signaling to protect from lymphedema. Arterioscler. Thromb. Vasc. Biol. 2018; 38: 1346-1357 Crossref PubMed Scopus (37) Google Scholar ]. However, clinical trials of the Woman’s Health Initiative (WHI) have confirmed an increased risk of breast cancer in women using HRT. Furthermore, many patients with breast cancer have secondary lymphedema as a side effect of sentinel lymph node biopsies taken during cancer surgery or treatment with the antiestrogenic drug tamoxifen [ [2] Morfoisse F. Tatin F. Chaput B. Therville N. Vaysse C. Metivier R. et al. Lymphatic vasculature requires estrogen receptor-alpha signaling to protect from lymphedema. Arterioscler. Thromb. Vasc. Biol. 2018; 38: 1346-1357 Crossref PubMed Scopus (37) Google Scholar ]. Thus, there is a need for alternative therapies for lymphedema to improve the quality of life of postmenopausal women, as well as cancer patients.