Helske Satu, Syväranta Suvi, Lindstedt Ken A, Lappalainen Jani, Oörni Katariina, Mäyränpää Mikko I, Lommi Jyri, Turto Heikki, Werkkala Kalervo, Kupari Markku, Kovanen Petri T
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland.
Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1791-8. doi: 10.1161/01.ATV.0000228824.01604.63. Epub 2006 May 25.
To investigate the possible role of elastolytic cathepsins S, K, and V and their endogenous inhibitor cystatin C in adverse extracellular matrix remodeling of stenotic aortic valves.
Stenotic aortic valves were collected at valve replacement surgery and control valves at cardiac transplantations. The expression of cathepsins S, K, and V and cystatin C was studied by conventional and real-time polymerase chain reaction and by immunohistochemistry. Total cathepsin activity in the aortic valves was quantified by a fluorometric microassay. When compared with control valves, stenotic valves showed increased mRNA expression of cathepsins S, K, and V (P<0.05 for each) and a higher total cathepsin activity (P<0.001). In stenotic valves, cystatin C mRNA was increased (P<0.05), and cystatin C protein was found particularly in areas with infiltrates of inflammatory cells. Both cathepsin S and cystatin C were present in bony areas of the valves, whereas cathepsin V localized to endothelial cells in areas rich of neovascularization. Incubation of thin sections of aortic valves with cathepsins S, K, and V resulted in severe disruption of elastin fibers, and this cathepsin effect could be blocked by adding cystatin C to the incubation system.
Stenotic aortic valves show increased expression and activity of elastolytic cathepsins S, K, and V. These cathepsins may accelerate the destruction of aortic valvular extracellular matrix, so promoting the progression of aortic stenosis.
研究弹性蛋白酶组织蛋白酶S、K和V及其内源性抑制剂胱抑素C在狭窄主动脉瓣不良细胞外基质重塑中的可能作用。
在瓣膜置换手术时收集狭窄主动脉瓣，并在心脏移植时收集对照瓣膜。通过传统和实时聚合酶链反应以及免疫组织化学研究组织蛋白酶S、K和V以及胱抑素C的表达。通过荧光微量测定法定量主动脉瓣中的总组织蛋白酶活性。与对照瓣膜相比，狭窄瓣膜显示组织蛋白酶S、K和V的mRNA表达增加（每种均P<0.05）以及总组织蛋白酶活性更高（P<0.001）。在狭窄瓣膜中，胱抑素C mRNA增加（P<0.05），并且胱抑素C蛋白尤其在有炎性细胞浸润的区域被发现。组织蛋白酶S和胱抑素C均存在于瓣膜的骨化区域，而组织蛋白酶V定位于富含新生血管的区域的内皮细胞中。用组织蛋白酶S、K和V孵育主动脉瓣薄片导致弹性纤维严重破坏，并且通过向孵育系统中添加胱抑素C可以阻断这种组织蛋白酶效应。
狭窄主动脉瓣显示弹性蛋白酶组织蛋白酶S、K和V的表达和活性增加。这些组织蛋白酶可能加速主动脉瓣细胞外基质的破坏，从而促进主动脉狭窄的进展。
