Molecular Cardiovascular Research Program, Sarver Heart Center, Department of Physiology, University of Arizona, Tucson, AZ 85724, USA.
J Mol Cell Cardiol. 2011 Sep;51(3):428-34. doi: 10.1016/j.yjmcc.2011.06.006. Epub 2011 Jun 16.
Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this mechanism contributes to viscosity in vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in vivo via an integrative physiological study on a unique PEVK knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30-40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in vivo and shows that PEVK-actin interactions are an important physiological source of viscosity.
黏度被认为可以调节舒张功能，但人们对黏度的来源知之甚少。体外实验表明，连接蛋白titin 的脯氨酸-谷氨酸-缬氨酸-赖氨酸（PEVK）富含区与肌动蛋白相互作用，在肌节中产生粘性力。目前尚不清楚该机制是否有助于体内的黏度。我们通过对一种独特的 PEVK 敲除（KO）模型进行综合生理研究，检验了 PEVK-肌动蛋白相互作用导致心脏黏度的假设，并检验了其在体内的重要性。我们从野生型（WT）和 PEVK KO 小鼠中分离出去皮心肌细胞和乳头肌纤维，并使用拉伸保持释放和正弦波分析来检测被动黏度。在室温下，KO 心肌细胞和肌肉纤维的黏度分别降低了约 60%和 50%。PEVK-肌动蛋白相互作用不受温度或舒张钙的调节，但受晶格压缩的调节。在完整的分离的小鼠心脏上进行的拉伸保持和正弦波频率方案显示，黏度降低了 30-40%，这可能是由于肌球蛋白的相互作用，并且表明微管不参与黏度的形成。经二尖瓣多普勒超声心动图也同样显示，在体内的 PEVK KO 中 LV 腔黏度降低了 40%。这项综合研究首次定量评估了特定分子（PEVK-肌动蛋白）在体内对黏度的影响，并表明 PEVK-肌动蛋白相互作用是黏度的一个重要生理来源。
