Matrix metalloproteinase-2 is associated with tenascin-C in calcific aortic stenosis.
We previously showed that the expression of tenascin (TN-C), an extracellular matrix glycoprotein found in developing bone and atherosclerotic plaque, and matrix metalloproteinase-2 (MMP-2) are coordinated and interdependent in cultured vascular smooth muscle cells. In this study, we hypothesized that TN-C and MMP-2 are mechanistically involved in the pathobiology of calcific aortic stenosis. Human calcific aortic stenosis cusps demonstrated immunohistochemically prominent deposition of TN-C, MMP-2, and alkaline phosphatase activity, as well as MMP-2 gelatinolytic activity. Although far lesser amounts of TN-C were noted in several of the grossly non-calcified valve cusps, MMP-2 and AP were never detected. Further, when aortic valve interstitial cells (both sheep and human) were cultivated on collagen supplemented with TN-C, both MMP-2 mRNA expression and MMP-2 gelatinolytic activity (both pro and active forms), were up-regulated compared to control. These observations support the view that accumulation of first TN-C and then MMP-2 are associated with progression of calcification. The residual presence of these proteins in severe calcifications is indicative of their involvement in the pathogenesis.
Jian
B
B
Cardiology Research Laboratory, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA.
Jones
P L
PL
Li
Q
Q
Mohler
E R
ER
Schoen
F J
FJ
Levy
R J
RJ
D000818:Animals; D001021:Aortic Valve / Q000378:metabolism; D001024:Aortic Valve Stenosis / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D019063:Tenascin / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D019063:Tenascin; D020778:Matrix Metalloproteinase 2