LAUSR

Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure of Z25 mmHg at rest, which is determined by right heart catheterization [1]. The condition is further characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and death [2]. The clinical classification of PH categorizes multiple clinical conditions into five groups according to clinical presentation/etiology, histologic findings, hemodynamic characteristics and treatment strategy. These groups are fully described in the most recent European Society of Cardiology/European Respiratory Society guidelines [1]. The pathophysiology of PH is complex and in many respects heterogeneous, and underlined by multiple molecular pathways [1], which are not well understood [2,3]. In the light of this, current PH therapies should ideally, target all major molecular pathways (where possible), in order to eradicate PH or limit its progression. However, current therapies only target certain pathways and thus have a modest impact on PH patient mortality [1,2]. Exploration of PH through the use of animal models is imperative and may aid in the development of improved treatments [2,4]. The natural evolution of biomedical research is that basic research is translated from bench-to-bedside. However, this either does not occur or is impeded by factors such as the lack of animal models recapitulating clinical features of PH [4]. Although not the only reason; the lack of this recapitulation explain why experimental therapies tested in animals often lead to the abolishment or reversal of PH, but rarely translate to the clinical setting. Therefore with good reason, legitimate concern has been raised pertaining the shortfalls of animal models, and their relevance in PH research [5,6]. One might ask: Is it truly necessary for animal models to recapitulate clinical features of PH? The answer might vary within the scientific community. However, if they do not recapitulate clinical PH, no reasonable scientific grounds exist for the translation of findings made in a particular animal model, to the clinical setting. Therefore, if an animal model is created to mimic group-one PH, it should display precapillary PH with the relevant changes in mean pulmonary artery pressure, pulmonary arterial wedge pressure, and histopathologic features [1]. Furthermore, considering the numerous PH groups: Which type of PH does the animal model represent? This is an important question, because animal models with undefined PH, may cast doubt on the clinical relevance of findings. Bluntly asked, if humans rarely develop group 5 and 3 PH simultaneously, why should