Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
107-252 |
DRI_Background |
denotes |
Calcified aortic valve (AV) cusps have increased expression of bone morphogenic proteins (BMPs) and transforming growth factor-beta1 (TGF-beta1). |
T2 |
253-379 |
DRI_Approach |
denotes |
Elevated stretch loading on the AV is known to increase expression of matrix remodeling enzymes and pro-inflammatory proteins. |
T3 |
380-482 |
DRI_Background |
denotes |
Little, however, is known about the mechanism by which elevated stretch might induce AV calcification. |
T4 |
483-596 |
DRI_Approach |
denotes |
We investigated the hypothesis that elevated stretch may cause valve calcification via a BMP-dependent mechanism. |
T5 |
597-911 |
DRI_Outcome |
denotes |
Porcine AV cusps were cultured in a stretch bioreactor, at 10% (physiological) or 15% (pathological) stretch and 70 beats per minute for 3, 7, and 14 days, in osteogenic media supplemented with or without high phosphate (3.8 mmol/L), TGF-beta1 (1 ng/ml), as well as the BMP inhibitor noggin (1, 10, and 100 ng/ml). |
T6 |
912-943 |
DRI_Approach |
denotes |
Fresh cusps served as controls. |
T7 |
944-1148 |
DRI_Outcome |
denotes |
Alizarin red and von Kossa staining demonstrated that 15% stretch elicited a stronger calcification response compared with 10% stretch in a fully osteogenic medium containing high phosphate and TGF-beta1. |
T8 |
1149-1284 |
DRI_Background |
denotes |
BMP-2, -4, and Runx2 expression was observed after 3 days on the fibrosa surface of the valve cusp and was stretch magnitude-dependent. |
T9 |
1285-1331 |
DRI_Background |
denotes |
Cellular apoptosis was highest at 15% stretch. |
T10 |
1332-1490 |
DRI_Background |
denotes |
Tissue calcium content and alkaline phosphatase activity were similarly stretch-dependent and were significantly reduced by noggin in a dose dependent manner. |
T11 |
1491-1588 |
DRI_Challenge |
denotes |
These results underline the potential role of BMPs in valve calcification due to altered stretch. |