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Abstract

Abstract

The mechanical properties of heart valves are modulated by the contractile response of valve interstitial cells (VICs). It is unknown how the contractile responses of VICs are translated to the extra cellular matrix to alter the stiffness of the valve tissue. We have studied the signalling mechanisms of integrin subunits and specifically α2β1 integrin, a predominant collagen binding molecule, in mediating the contractility of porcine mitral valve tissue and cells. The expression of integrins was analysed by immunostaining of cells. The contractility of porcine mitral VICs in the presence and absence of a α2β1 integrin blocking antibody and the effect of different signalling inhibitors was analysed in a collagen gel. The effect of modulators of contractility was determined on mitral valve tissue incubated in organ baths which challenged with endothelin-1 (10-10-10-7M) following 24 hours incubation with α2β1 integrin blocking antibody. Immunohistochemistry confirmed positive staining for α2β1 integrin and the expression of α1, α2, α3 and β1 in the VICs. The α2β1 blocking antibody was able to significantly reduce the contraction of collagen gels from 63.6±7.8 to 23.4±4.3 % (p<0.001) of control (no cells in gel). PF573228, the inhibitor of focal adhesion kinase, caused a reduction of gel contraction by 30% of the control. The maximum contractile response of cusp tissue to ET-1 maintained under isometric conditions in tissue baths was significantly reduced from 9.5±5.0 to 3.0±2.5mN/g (p<0.001) wet weight by the presence of the α2β1 integrin blocking antibody. These results demonstrate a role for α2β1 integrin in linking the contractile response of valve cells to the extra cellular matrix and highlight further the complex interactions between the cells and the extra cellular matrix of the valve.

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/content/papers/10.5339/qproc.2012.heartvalve.4.5
2012-05-01
2019-11-14
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.heartvalve.4.5
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  • Accepted: 24 May 2012
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