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Potential novel role of the immune system in the pathogenesis of myxomatous mitral valve disease
Author(s) -
Thalji Nassir M,
Hagler Michael A,
Suri Rakesh M,
Miller Jordan D
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.386.11
Subject(s) - immune system , cd14 , fibrosis , biology , chemokine , immunology , cx3cr1 , disease , medicine , chemokine receptor , pathology
Myxomatous mitral valve disease (MMVD), if untreated, progresses to valve prolapse, mitral regurgitation, and heart failure. Molecular mechanisms contributing to MMVD are poorly understood, and surgery remains the primary treatment for this disease. In the current study, we used whole‐genome expression microarrays in normal (n = 12) and myxomatous (n = 11) mitral valves as a nonbiased approach to identify novel pathways contributing to MMVD. In addition to identifying known contributors to fibrosis in MMVD (e.g. TGFβ signaling), we found robust evidence of immune cell infiltration and activation in myxomatous valves. Specifically, toll‐like receptors (TLRs) 3 and 7, which play a key role in antigen recognition, alongside cell surface receptors CD14 and CD83, characteristic of antigen presenting cells of monocytic lineage, were overexpressed in myxomatous tissue. Interleukin‐7 and the chemokine receptor CX3CR1, implicated in monocyte activation and recruitment, were also upregulated. Interestingly, immune localization appeared independent of “classic” inflammatory cytokines such as IL‐6. Differential expression of a subset of genes was confirmed with qRT‐PCR and immunohistochemistry. In conclusion, these data are the first to demonstrate infiltration of immune cells in MMVD, which may represent a critical process in the initiation and/or progression of this disease. NHLBI