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Differential expression patterns of Toll Like Receptors and Interleukin-37 between calcific aortic and mitral valve
Alkistis Kapelouzou1, Christos Kontogiannis2, Diamantis I Tsilimigras2
1Centre for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Insights
Aortic and mitral valve calcification differ due to inflammation. Aortic valves show lower Interleukin-37 (IL-37) and higher Toll Like Receptors (TLR) than mitral valves, impacting calcification progression.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathology
Background:
- Calcific valve disease involves inflammation, with Toll Like Receptors (TLR) and Interleukin-37 (IL-37) pathways implicated.
- Significant differences exist in calcification progression between aortic and mitral valves.
Purpose of the Study:
- To investigate the role of TLR-mediated inflammation and IL-37 pathway expression in aortic and mitral valve calcification.
- To compare the expression of inflammatory markers and calcification biomarkers between stenotic aortic and mitral valves.
Main Methods:
- Histological, immunohistochemistry, and morphometric analysis of 120 stenotic valve cusps (60 aortic, 60 mitral).
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) to assess mRNA levels of target genes.
Main Results:
- Mitral valve leaflets (MVL) showed increased anti-inflammatory IL-37 levels compared to aortic valve cusps (AVCu).
- Toll Like Receptors (TLR) levels were decreased in MVL compared to AVCu.
- Osteopontin was the only calcification biomarker that differed between AVCu and MVL.
Conclusions:
- Stenotic aortic valves exhibit lower IL-37 and higher TLR levels than stenotic mitral valves, indicating distinct pro-calcification and pro-inflammatory profiles.
- These differential inflammatory profiles may explain the higher incidence of aortic valve calcification and suggest potential therapeutic targets.
Background:
Significant differences are mentioned in the progress of calcification between aortic and mitral valve. Evidence of inflammation in calcific aortic and mitral valve disease suggests that pathways of Toll Like Receptors (TLR) and Interleukin (IL)-37 expression may contribute to this process. We sought to investigate the role of TLR-mediated inflammatory response and IL-37 pathway expression on aortic and mitral valve calcification.
Material And Methods:
One-hundred twenty stenotic valve cusps/leaflets (60 aortic, 60 mitral) were excised during surgery and were collected for histological, immunohistochemistry and morphometric analysis at our department. After total RNA isolation from a second part of valve cusps/leaflets, cDNA synthesis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) protocols were performed and relative mRNA levels of target genes were assessed.
Results:
By histological analysis, the anti-inflammatory IL-37 levels were increased in mitral valve leaflets (MVL) compared to aortic valve cusps (AVCu) while all other biomarkers, including TLR, presented a reverse pattern with decreased levels as compared to AVCu. In terms of calcification biomarkers, only osteopontin differed between AVCu and MVL. mRNA analysis confirmed increased expression of IL-37 and decreased levels of TLR in MVL compared to AVCu.
Conclusions:
Stenotic cusps of aortic valves express lower IL-37 and increased TLRs levels than stenotic mitral valve leaflets, suggesting a differential pro-calcification and pro-inflammatory profile between the two valves. This may explain the higher incidence of calcification of AVCu than MVL and offer therapeutic considerations.
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