Key result
Current animal models fail to fully replicate adult PH, requiring multi-hit approaches to improve translation.
Why the study?
Animal models are essential to understand molecular mechanisms and test new therapies for pulmonary hypertension, but limitations hinder full recapitulation of human disease and clinical translation.
This review highlights the strengths and limitations of current animal models for pulmonary hypertension and suggests multi-hit approaches to improve clinical translation.
Current PH animal models have limited translational fidelity; multi-hit refinements require prospective validation before informing trials.
Pulmonary hypertension (PH) describes heterogeneous population of patients with a mean pulmonary arterial pressure >20 mm Hg. Rarely, PH presents as a primary disorder but is more commonly part of a complex phenotype associated with comorbidities. Regardless of the cause, PH reduces life expectancy and impacts quality of life. The current clinical classification divides PH into 1 of 5 diagnostic groups to assign treatment. There are currently no pharmacological cures for any form of PH. Animal models are essential to help decipher the molecular mechanisms underlying the disease, to assign genotype-phenotype relationships to help identify new therapeutic targets, and for clinical translation to assess the mechanism of action and putative efficacy of new therapies. However, limitations inherent of all animal models of disease limit the ability of any single model to fully recapitulate complex human disease. Within the PH community, we are often critical of animal models due to the perceived low success upon clinical translation of new drugs. In this review, we describe the characteristics, advantages, and disadvantages of existing animal models developed to gain insight into the molecular and pathological mechanisms and test new therapeutics, focusing on adult forms of PH from groups 1 to 3. We also discuss areas of improvement for animal models with approaches combining several hits to better reflect the clinical situation and elevate their translational value.
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Boucherat et al. (2022) conducted a review in Pulmonary hypertension. Animal models was evaluated. Existing animal models for adult pulmonary hypertension (groups 1 to 3) have inherent limitations in fully recapitulating complex human disease, necessitating multi-hit approaches to improve translation.
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