Animal models of pulmonary hypertension: Getting to the heart of the problem.
Joshua P DignamTara Elizabeth ScottBarbara K Kemp-HarperAdrian J HobbsPublished in: British journal of pharmacology (2021)
Despite recent therapeutic advances, pulmonary hypertension (PH) remains a fatal disease due to the development of right ventricular (RV) failure. At present, no treatments targeted at the right ventricle are available, and RV function is not widely considered in the preclinical assessment of new therapeutics. Several small animal models are used in the study of PH, including the classic models of exposure to either hypoxia or monocrotaline, newer combinational and genetic models, and pulmonary artery banding, a surgical model of pure RV pressure overload. These models reproduce selected features of the structural remodelling and functional decline seen in patients and have provided valuable insight into the pathophysiology of RV failure. However, significant reversal of remodelling and improvement in RV function remains a therapeutic obstacle. Emerging animal models will provide a deeper understanding of the mechanisms governing the transition from adaptive remodelling to a failing right ventricle, aiding the hunt for druggable molecular targets.
Keyphrases
- pulmonary hypertension
- pulmonary artery
- mycobacterium tuberculosis
- pulmonary arterial hypertension
- end stage renal disease
- coronary artery
- newly diagnosed
- chronic kidney disease
- ejection fraction
- prognostic factors
- small molecule
- peritoneal dialysis
- heart failure
- patient reported outcomes
- atrial fibrillation
- genome wide
- bone marrow