Balsa, A.; Adão, R.; Brás-Silva, C. Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function—Preclinical Studies. Int. J. Mol. Sci.2023, 24, 15539.
Balsa, A.; Adão, R.; Brás-Silva, C. Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function—Preclinical Studies. Int. J. Mol. Sci. 2023, 24, 15539.
Balsa, A.; Adão, R.; Brás-Silva, C. Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function—Preclinical Studies. Int. J. Mol. Sci.2023, 24, 15539.
Balsa, A.; Adão, R.; Brás-Silva, C. Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function—Preclinical Studies. Int. J. Mol. Sci. 2023, 24, 15539.
Abstract
Pulmonary hypertension (PH) is a progressive condition that affects pulmonary vessels, but its main prognostic factor is right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate in clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and RV structure and function in PAB animals. PH models and PAB frequently exhibited similar results (73.1% concordance) with drugs other than endothelin receptor antagonists and phosphodiesterase inhibitors. RV systolic pressure accounted for most differences between PH models and PAB. On the other side, all results on RV fibrosis agreed (12 drugs). Macitentan, sildenafil and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Dapagliflozin was the only drug that improved no parameters. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. To improve the translational potential of drugs in this field, researchers should test them in multiple models, including PAB, while optimizing induction methods for human disease translation.
Keywords
pulmonary arterial hypertension; pulmonary arterial banding; right ventricle; preclinical studies
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.