CLINICAL STUDY
Progression of human aortic valve stenosis is associated with tenascin-C expression
Jari Satta, MD, PhD*,*,
Jukka Melkko, MD, PhD ,
Raimo Pöllänen, PhD,
Juha Tuukkanen, DDS, PhD ,
Paavo Pääkkö, MD, PhD,
Pasi Ohtonen, MSc*,
Ari Mennander, MD, PhD* and
Ylermi Soini, MD, PhD
* Department of Surgery, University of Oulu and Oulu University Hospital, Oulu, Finland
Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland
Department ofAnatomy and Cell Biology, University of Oulu and Oulu University Hospital, Oulu, Finland
Manuscript received April 6, 2001;
revised manuscript received August 27, 2001,
accepted September 7, 2001.
* Reprint requests and correspondence: Dr. Jari Satta, Department of Cardiothoracic Surgery, University of Oulu, Kajaanintie 52 A, FIN-90220 Oulu, Finland.
jari.satta{at}oulu.fi
OBJECTIVES: We sought to assess tenascin-C (TN-C) expression and its possible pathobiological impact in human aortic valve stenosis.
BACKGROUND: Tenascin-C, a large extracellular matrix glycoprotein, has lately been increasingly connected to cardiovascular pathologies. As TN-C is a multifunctional protein implicated in cell proliferation, migration and differentiation, we investigated the pattern of its expression in diseased human aortic valves.
METHODS: Fifty-five tricuspid, non-rheumatic stenotic aortic valves were collected from patients undergoing aortic valve replacement, and the controls consisted of four normal valves from individuals who had suffered traumatic death and one from a patient operated on because of a noncalcified purely regurgitant valve. A monoclonal mouse antibody to human TN-C (143DB7) was used as the primary antibody in immunostaining. To study the source of TN-C messenger RNA synthesis, some tissue samples were also examined using in situ hybridization. In order to identify smooth muscle cell differentiation, commercially available antibodies against alpha-smooth muscle actin were used, and immunophenotypic analysis of inflammatory cells was carried out by using the monoclonal mouse antibodies UCHL-1, L26 and PGM-1.
RESULTS: In normal valves, TN-C expression was associated with the basement membrane beneath the endothelial cells, whereas stenotic valves showed no such expression but rather immunoreactivity in the deeper layers of the valves. This reactivity was associated with the characteristics typical of the stenosing process and the increased mechanical loading caused by hypertension.
CONCLUSIONS: We hypothesize that the overexpression of TN-C in stenotic human aortic valves may emphasize that this disease is an active rather than a degenerative process.
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Abbreviations and Acronyms
| | cDNA | | complementary DNA | | EC | | endothelial cell | | ECM | | extracellular matrix | | MMP | | matrixmetalloproteinase | | mRNA | | messenger RNA | | PCR | | polymerase chain reaction | | TGF-beta | | transforming growth factor-beta | | TN-C | | tenascin-C |
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