Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
Animal Model Exp Med. 2022 Sep;5(3):197-206. doi: 10.1002/ame2.12214. Epub 2022 Feb 9.
Pulmonary hypertension due to left heart disease (PH-LHD) is regarded as the most prevalent form of pulmonary hypertension (PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease (LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.
由左心疾病（PH-LHD）引起的肺动脉高压被认为是最常见的肺动脉高压（PH）形式。事实上，PH 是左心疾病（LHD）患者的独立危险因素，并预测不良预后。临床上，没有药物或治疗方法可以直接针对 PH-LHD，单独治疗 LHD 也不会改善 PH。为了针对 PH-LHD 的潜在病理生理改变，并为该人群开发新的治疗方法，需要模拟 PH-LHD 病理生理学的动物模型。有几种可用于 PH-LHD 的模型已经在啮齿动物或大型动物中成功应用，通过人为地对左心施加升高的压力负荷，从而在肺动脉中引起升高的压力。此外，代谢紊乱结合主动脉缩窄或血管内皮生长因子受体拮抗剂也可用于重现 PH-LHD 的表型。截至今天，没有一种动物模型能完全重现 PH-LHD 患者的情况。然而，选择合适的动物模型对于 PH-LHD 的基础和转化研究至关重要。因此，本综述将总结每种 PH-LHD 动物模型的特点，并讨论不同模型的优缺点。
