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Phenotypic modulation of smooth muscle cells in lymphoedema
Author(s) -
Ogata F.,
Fujiu K.,
Koshima I.,
Nagai R.,
Manabe I.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13482
Subject(s) - phenotype , medicine , modulation (music) , biology , genetics , physics , gene , acoustics
Summary Background Lymphoedema is a debilitating progressive condition that is frequently observed following cancer surgery and severely restricts quality of life. Although it is known that lymphatic dysfunction and obstruction underlie lymphoedema, the pathogenic mechanism is poorly understood. Smooth muscle cells ( SMC s) play pivotal roles in the pathogenesis of various vascular diseases, including atherosclerosis. Objectives We analysed SMC s in lymphatic vessels from the lymphoedematous legs of 29 patients. Methods Expression of smooth muscle α‐actin ( SM αA) and smooth muscle myosin heavy chain ( SM ‐ MHC ) isoforms SM 1 and SM 2 was investigated using immunohistochemistry. Results Compared with normal lymphatic vessels, all affected lymphatic vessels in chronic lymphoedema showed marked wall thickening. In addition to increases in the numbers of rows of SM αA + SM 1 + SMC s in the tunica media, SMC s were also observed in the subendothelial region (tunica intima). While most intimal and medial cells were positive for SM αA and SM 1, staining for SM 1 and particularly SM 2, a marker of mature SMC s, progressively declined in lymphatic vessels in increasingly severe lymphoedema lesions. Consequently, the SM 1 + and SM 2 + cell fractions were significantly reduced in the tunica media and intima of lymphatic vessels. Conclusions These observations indicate that the lymphatic tunica media and tunica intima consist mainly of phenotypically modulated SMC s, and that SMC s play a key role in the development of lymphoedema.