Animal models of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, yet life-threatening disorder characterized by persistent pulmonary vascular obstruction and elevated pulmonary artery pressure, with progressive remodeling and subsequent right heart failure. Despite substantial progress in elucidating the pathophysiology of CTEPH, the molecular mechanisms driving disease initiation and progression remain incompletely defined. Bridging these knowledge gaps and enabling the development of CTEPH-specific therapeutic strategies depend on experimental models that faithfully recapitulate the key pathological features observed in patients. A wide range of small- and large-animal models has therefore been established to mimic CTEPH development, each offering specific strengths and inherent limitations. Small animal models are relatively inexpensive, readily amenable to genetic manipulation, and well suited for high-throughput mechanistic investigations. However, their capacity to reproduce the complex pulmonary vascular architecture and hemodynamic characteristics of human disease is limited. By comparison, large-animal models more closely approximate human pulmonary anatomy and cardiovascular physiology, making them particularly valuable for detailed hemodynamic measurements and advanced imaging studies. Their broader application, however, is constrained by high financial costs, ethical considerations, and the need for specialized surgical and monitoring techniques. In this review, we provide an overview of currently available animal models of CTEPH, with emphasis on their methodological features, their ability to reproduce clinically relevant disease characteristics, and their potential utility in preclinical and translational research.