Platt Manu O, Xing Yun, Jo Hanjoong, Yoganathan Ajit P
The Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
J Heart Valve Dis. 2006 Sep;15(5):622-9.
It has been shown previously that the exposure of porcine aortic valve leaflets (PAVL) to elevated pressure or steady shear stress increases extracellular matrix (ECM) synthesis. It was hypothesized that exposure of the aortic valves to pressure or shear stress would regulate valvular expression of proteases such as matrix metalloproteinases (MMPs) and cathepsins.
Fresh PAVLs were exposed to cyclic pressure (170 mmHg at 1.167 Hz) or to a steady shear stress of 25 dyne/cm2 for 48 h, with static culture serving as controls.
Shear stress significantly inhibited cathepsin activity and cathepsin L protein expression, but increased MMP-2/9 activity. A cyclic hypertensive pressure condition also slightly decreased MMP-2/9 and cathepsin L activities.
For the first time, valvular cathepsin and MMP activity were seen to be directly regulated by mechanical forces such as pressure and shear stress. The down-regulation of cathepsin L activity correlates with an up-regulation of ECM synthesis; MMP-2 and -9 activities increased with ECM synthesis under shear stress, showing that these proteinases may serve different roles in valvular remodeling. This observation may have implications for understanding valve biology, as well as for valve tissue engineering.
先前的研究表明，猪主动脉瓣叶（PAVL）暴露于升高的压力或稳定的剪切应力下会增加细胞外基质（ECM）的合成。据推测，主动脉瓣暴露于压力或剪切应力下会调节诸如基质金属蛋白酶（MMPs）和组织蛋白酶等蛋白酶的瓣膜表达。
将新鲜的PAVL暴露于循环压力（170 mmHg，频率为1.167 Hz）或25达因/平方厘米的稳定剪切应力下48小时，静态培养作为对照。
剪切应力显著抑制组织蛋白酶活性和组织蛋白酶L蛋白表达，但增加MMP-2/9活性。循环高血压压力条件也略微降低MMP-2/9和组织蛋白酶L活性。
首次发现瓣膜组织蛋白酶和MMP活性可直接受压力和剪切应力等机械力的调节。组织蛋白酶L活性的下调与ECM合成的上调相关；在剪切应力下，MMP-2和-9活性随ECM合成增加，表明这些蛋白酶在瓣膜重塑中可能发挥不同作用。这一观察结果可能对理解瓣膜生物学以及瓣膜组织工程具有重要意义。
