Luitel Himal, Sydykov Akylbek, Schymura Yves, Mamazhakypov Argen, Janssen Wiebke, Pradhan Kabita, Wietelmann Astrid, Kosanovic Djuro, Dahal Bhola Kumar, Weissmann Norbert, Seeger Werner, Grimminger Friedrich, Ghofrani Hossein Ardeschir, Schermuly Ralph Theo
Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center Member of the German Lung Center Justus-Liebig-University Giessen, Giessen, Germany.
Department of Lung Development and Remodelling, Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Physiol Rep. 2017 Mar;5(6). doi: 10.14814/phy2.13146.
Right ventricular (RV) remodeling represents a complex set of functional and structural adaptations in response to chronic pressure or volume overload due to various inborn defects or acquired diseases and is an important determinant of patient outcome. However, the underlying molecular mechanisms remain elusive. We investigated the time course of structural and functional changes in the RV in the murine model of pressure overload-induced RV hypertrophy in C57Bl/6J mice. Using magnetic resonance imaging, we assessed the changes of RV structure and function at different time points for a period of 21 days. Pressure overload led to significant dilatation, cellular and chamber hypertrophy, myocardial fibrosis, and functional impairment of the RV Progressive remodeling of the RV after pulmonary artery banding (PAB) in mice was associated with upregulation of myocardial gene markers of hypertrophy and fibrosis. Furthermore, remodeling of the RV was associated with accumulation and activation of mast cells in the RV tissue of PAB mice. Our data suggest possible involvement of mast cells in the RV remodeling process in response to pressure overload. Mast cells may thus represent an interesting target for the development of new therapeutic approaches directed specifically at the RV.
右心室（RV）重塑是一组复杂的功能和结构适应性变化，是对各种先天性缺陷或后天性疾病导致的慢性压力或容量超负荷的反应，是患者预后的重要决定因素。然而，其潜在的分子机制仍不清楚。我们在C57Bl/6J小鼠压力超负荷诱导的右心室肥大小鼠模型中研究了右心室结构和功能变化的时间进程。使用磁共振成像，我们在21天的时间内评估了不同时间点右心室结构和功能的变化。压力超负荷导致右心室显著扩张、细胞和腔室肥大、心肌纤维化以及功能损害。小鼠肺动脉环扎（PAB）后右心室的进行性重塑与肥大和纤维化的心肌基因标志物上调有关。此外，右心室重塑与PAB小鼠右心室组织中肥大细胞的积聚和激活有关。我们的数据表明肥大细胞可能参与了对压力超负荷的右心室重塑过程。因此，肥大细胞可能是开发专门针对右心室的新治疗方法的一个有趣靶点。
