Pulmonary Pharmacotherapy, Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary System (ECCPS), Member of German Center for Lung Research, Giessen, Germany.
Exp Physiol. 2013 Aug;98(8):1274-8. doi: 10.1113/expphysiol.2012.069138.
Pulmonary arterial hypertension (PAH) is a progressive disease that is associated with a poor prognosis and results in right heart dysfunction. While pulmonary vascular disease is the obvious primary pathological focus, right ventricular hypertrophy (RVH) and right ventricular (RV) dysfunction are major determinants of prognosis in PAH. Our knowledge about the molecular physiology and pathophysiology of RV hypertrophy and failure in response to pressure overload is still limited, and most data are derived from left heart research. However, the molecular mechanisms of left ventricular remodelling cannot be generalized to the RV, because the right and left ventricles differ greatly in their size, shape, architecture and function. Despite the recent advances in diagnosis and treatment of PAH, little is known about the molecular and cellular mechanisms that underlie the transition from compensatory to maladaptive RV remodelling. The cGMP-phosphodiesterase 5 (PDE5) pathway is one of the extensively studied pathways in PAH, but our knowledge about cGMP-PDE5 signalling in RV pathophysiology is still limited. For this purpose, there is need for animal models that can represent changes in the RV that closely mimic the human situation. The availability of an animal model of pressure-overload-induced RVH (e.g. pulmonary artery banding model) provides us with a valuable tool to understand the differences between adaptive and maladaptive RVH and to explore the direct effects of current PAH therapy on the heart. In this report, we discuss myocardial regulatory effects of cGMP-PDE5 signalling in preclinical models of RV pressure overload for understanding the physiological/pathophysiological mechanisms involved in maladaptive RVH.
肺动脉高压（PAH）是一种进行性疾病，预后不良，导致右心功能障碍。虽然肺血管疾病是明显的主要病理焦点，但右心室肥厚（RVH）和右心室（RV）功能障碍是 PAH 预后的主要决定因素。我们对 RV 肥厚和对压力超负荷反应的功能障碍的分子生理学和病理生理学的了解仍然有限，并且大多数数据来自于左心研究。然而，左心室重构的分子机制不能推广到 RV，因为右心室和左心室在大小、形状、结构和功能上有很大的不同。尽管 PAH 的诊断和治疗最近取得了进展，但对于导致从代偿性 RV 重构向适应性不良 RV 重构转变的分子和细胞机制知之甚少。cGMP-磷酸二酯酶 5（PDE5）途径是 PAH 中研究最广泛的途径之一，但我们对 RV 病理生理学中 cGMP-PDE5 信号的了解仍然有限。为此，需要能够代表 RV 变化的动物模型，这些变化与人类情况非常相似。压力超负荷诱导的 RVH 动物模型（例如肺动脉环扎模型）的可用性为我们提供了一个有价值的工具，可用于了解适应性和适应性不良 RVH 之间的差异，并探索当前 PAH 治疗对心脏的直接影响。在本报告中，我们讨论了 cGMP-PDE5 信号在 RV 压力超负荷的临床前模型中的心肌调节作用，以了解涉及适应性不良 RVH 的生理/病理生理机制。
