Right Ventricular Fibrosis: A Pathophysiological Factor in Pulmonary Hypertension?
Right Ventricular Fibrosis: A Pathophysiological Factor in Pulmonary Hypertension?
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DOI：
10.1161/circulationaha.118.035326
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发表时间：
2019-01-08
期刊：
影响因子：
37.8
通讯作者：
de Man, Frances S.
中科院分区：
文献类型：
--
作者：
Andersen, Stine;Nielsen-Kudsk, Jens Erik;de Man, Frances S.
右心室（RV）纤维化在肺动脉高压（PH）中的作用仍然是一个持续讨论的主题。细胞外基质胶原网络的改变可能有助于防止压力超负荷RV的心室扩张。同时，纤维化损害心脏功能，越来越多的实验数据表明，纤维化在RV衰竭的发展中起着至关重要的作用。在特发性肺动脉高压和慢性血栓栓塞性PH中，RV暴露于大约5倍增加的后负荷，这使得这些条件成为研究压力超负荷对RV结构影响的极好模型。通过这篇综述，我们提出了特发性肺动脉高压和慢性血栓栓塞性PH中RV纤维化的临床证据，探讨了纤维化与RV功能之间的相关性，并讨论了PH患者RV纤维化的临床相关性。我们假设RV纤维化在特发性肺动脉高压和慢性血栓栓塞性PH的压力超负荷RV患者中具有双重作用：作为适应性反应的一部分，以防止心肌细胞过度伸展并维持RV形状以实现最佳功能，以及作为适应不良反应的一部分，其增加舒张僵硬度，扰乱心肌细胞兴奋-收缩偶联，并破坏心肌收缩的协调。最后，我们讨论了潜在的新的治疗策略，并描述了更敏感的技术来量化RV纤维化，这可能是用来澄清RV纤维化和RV功能之间的因果关系，在未来的研究。
The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a approximate to 5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research.