Ormeloxifene, a selective estrogen receptor modulator, protects against pulmonary hypertension

Abdulkareem, Adam Olaitan; Tiwari, Priya; Lone, Zahid Rasool; Iqbal, Hina; Gupta, Satish C.; Jha, Rajesh; Chanda, Debabrata; Jagavelu, Kumaravelu; Hanif, Kashif

doi:10.1016/j.ejphar.2023.175558

Cited by 6 publications

(2 citation statements)

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“…It was recently shown that the expression of both classical ERs is decreased in hypoxic control human pulmonary artery SMCs and the lungs of female monocrotaline rats (Abdulkareem et al, 2023). On the other hand, ER‐α is exclusively up‐regulated in human pulmonary artery SMCs isolated from females with PAH, while ER‐β expression is increased in cells from male donors.…”

Section: Targeting Estrogen Receptors (Ers)mentioning

confidence: 99%

“…Tamoxifen was found to be less efficacious at reversing PH in BMPR2 mutant mice than dual therapy with anastrozole and fulvestrant (Chen et al, 2017) (Table 1) but remains attractive from a clinical perspective as it can be used in fertile women without inducing menopause (Colleoni & Munzone, 2015). Ormeloxifene, another selective ER modulator, was recently reported to have protective effects in male and female monocrotaline rats (Abdulkareem et al, 2023). A small randomised controlled trial of tamoxifen in PAH patients of both sexes is now recruiting (T3PAH; ClinicalTrials.gov identifier: NCT03528902) (Table 2), with a primary endpoint of change from baseline on tricuspid annular plane systolic excursion (TAPSE; an echocardiographic measure of RV systolic function).…”

Section: Targeting Estrogen Receptors (Ers)mentioning

confidence: 99%

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Pulmonary arterial hypertension: Sex matters

Dignam,

Sharma,

Stasinopoulos

et al. 2024

British J Pharmacology

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Pulmonary arterial hypertension (PAH) is a complex disease of multifactorial origin. Whilst registries have demonstrated that women are more susceptible to the disease, females with PAH have superior RV function and a better prognosis than their male counterparts, a phenomenon referred to as the ‘oestrogen paradox.’ Numerous pre‐clinical studies have investigated the involvement of sex hormones in PAH pathobiology, often with conflicting results. However, recent advances suggest that abnormal oestrogen synthesis, metabolism, and signalling underpin the sexual dimorphism of this disease. Other sex hormones, such as progesterone, testosterone, and dehydroepiandrosterone, may also play a role. Several non‐hormonal factors, including sex chromosomes and epigenetics, have also been implicated. Though the underlying pathophysiological mechanisms are complex, several compounds that modulate sex hormones levels and signalling are under investigation in PAH patients. Further elucidation of the oestrogen paradox will set the stage for the identification of additional therapeutic targets for this disease.

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Section: Targeting Estrogen Receptors (Ers)mentioning

confidence: 99%