Mineralocorticoid receptors in pulmonary hypertension and right heart failure: From molecular biology to therapeutic targeting

Pulmonary hypertension (PH) is a devastating condition characterized by pulmonary vascular remodelling, leading to progressive increase in pulmonary artery pressure and subsequent right ventricular failure. Aldosterone and the mineralocorticoid receptor (MR), a nuclear transcription factor, are key...

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Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 2022-03, Vol.231, p.107987-107987, Article 107987
Main Authors: Mamazhakypov, Argen, Hein, Lutz, Lother, Achim
Format: Article
Language:English
Subjects:
Aldosterone
Animals
Endothelial Cells
Heart failure
Heart Failure - drug therapy
Humans
Hypertension, Pulmonary - drug therapy
Mice
Mineralocorticoid Receptor Antagonists - pharmacology
Mineralocorticoid Receptor Antagonists - therapeutic use
Mineralocorticoid receptors
Molecular Biology
Pulmonary hypertension
Receptors, Mineralocorticoid
Right ventricle
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Summary:Pulmonary hypertension (PH) is a devastating condition characterized by pulmonary vascular remodelling, leading to progressive increase in pulmonary artery pressure and subsequent right ventricular failure. Aldosterone and the mineralocorticoid receptor (MR), a nuclear transcription factor, are key drivers of cardiovascular disease and MR antagonists are well-established in heart failure. Now, a growing body of evidence points at a detrimental role of MR in PH. Pharmacological MR blockade attenuated PH and prevented RV failure in experimental models. Mouse models with cell selective MR deletion suggest that this effect is mediated by MR in endothelial cells. While the evidence from experimental studies appears convincing, the available clinical data on MR antagonist use in patients with PH is more controversial. Integrated analysis of clinical data together with MR-dependent molecular alterations may provide insights why some patients respond to MRA treatment while others do not. Potential ways to identify MRA ‘responders’ include the analysis of underlying PH causes, stage of disease, or sex, as well as new biomarkers.
ISSN:0163-7258
1879-016X
DOI:10.1016/j.pharmthera.2021.107987