Selexipag for the treatment of pulmonary arterial hypertension

Sharma, Kamal

doi:10.1586/17476348.2016.1121103

Cited by 11 publications

(6 citation statements)

References 17 publications

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“…Hence, prostacyclin agonists and analogues are used to treat severe PAH. The most recent member of this drug class, selexipag, a selective prostacyclin receptor agonist, was approved by the Food and Drug Administration (FDA) for PAH in 2015 (Lau et al, 2017, Sharma, 2015.…”

Section: Prostacyclin Analoguesmentioning

confidence: 99%

The Role of Sex in the Pathophysiology of Pulmonary Hypertension

Docherty

Harvey

Mair

et al. 2018

Advances in Experimental Medicine and Biology

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Pulmonary arterial hypertension (PAH) is a progressive disease characterised by increased pulmonary vascular resistance and pulmonary artery remodelling as result of increased vascular tone and vascular cell proliferation, respectively. Eventually, this leads to right heart failure. Heritable PAH is caused by a mutation in the bone morphogenetic protein receptor-II (BMPR-II). Female susceptibility to PAH has been known for some time, and most recent figures show a female-to-male ratio of 4:1. Variations in the female sex hormone estrogen and estrogen metabolism modify FPAH risk, and penetrance of the disease in BMPR-II mutation carriers is increased in females. Several lines of evidence point towards estrogen being pathogenic in the pulmonary circulation, and thus increasing the risk of females developing PAH. Recent studies have also suggested that estrogen metabolism may be crucial in the development and progression of PAH with studies indicating that downstream metabolites such as 16α-hydroxyestrone are upregulated in several forms of experimental pulmonary hypertension (PH) and can cause pulmonary artery smooth muscle cell proliferation and subsequent vascular remodelling. Conversely, other estrogen metabolites such as 2-methoxyestradiol have been shown to be protective in the context of PAH. Estrogen may also upregulate the signalling pathways of other key mediators of PAH such as serotonin.

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Section: Prostacyclin Analoguesmentioning

confidence: 99%

The Role of Sex in the Pathophysiology of Pulmonary Hypertension

Docherty

Harvey

Mair

et al. 2018

Advances in Experimental Medicine and Biology

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“…Pulmonary sarcomatoid carcinoma (PSC) is a rare, poorly differentiated, and highly aggressive tumor entity accounting for less than 3% of non-small cell lung cancer (NSCLC) [ 1 ]. Early metastatic dissemination and resistance to conventional therapies result in a prognosis usually poorer than other lung cancers [ 2 ]. Recently, the targeting of immunologic checkpoints turned out to be a major breakthrough in oncology.…”

Section: Introductionmentioning

confidence: 99%

Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis

et al. 2018

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Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. Objectives and Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma. He received first- and second-line chemotherapy without any benefit. Since March 2016, he has been treated with the anti-PD1 agent nivolumab with a dramatic improvement of symptoms, disappearance of a brain lesion, and partial response on other metastatic sites. He tolerated the treatment well and is still responding after 22 months from the beginning. Results and Conclusions: In very lethal non-small cell lung cancer subtypes such as the sarcomatoid variants, high tumor burden and deteriorated general conditions should not preclude, at least in some cases, the use of immunotherapy. Anti-PD1 may also have a reliable role in disease control in the brain. Lastly, the strong rationale behind sarcomatoid histology should further prompt trials exploring immunotherapeutic approaches in this subset of non-small cell lung cancer.

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“…On the one hand, some reports have shown that activation of ERα directly upregulates the proliferation and migration rate of VECs and VSMCs, 31 and some evidence has shown that the prevalence of PAH in young women is significantly higher than that in men of the same age. 2,32 On the other hand, our results showed that the reduction in ERα protein expression caused by ovarian removal undoubtedly aggravated the condition of PAH rats, and the smooth muscle of the Model group rats showed a more pronounced proliferative phenotype. It seems that we should conclude that inhibition of ERα promotes the proliferation of PSMCs.…”

Section: Discussionmentioning

confidence: 68%

Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells

Meng

et al. 2023

Clinical Translational Sci

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Pulmonary arterial hypertension (PAH) is a pathophysiological state of abnormally elevated pulmonary arterial pressure caused by drugs, inflammation, toxins, viruses, hypoxia, and other risk factors. We studied the therapeutic effect and target of tetramethylpyrazine (tetramethylpyrazine [TMP]; ligustrazine) in the treatment of PAH and we speculated that dramatic changes in myocardin levels can significantly affect the progression of PAH. In vivo, the results showed that administration of TMP significantly prolonged the survival of PAH rats by reducing the proliferative lesions, right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and the Fulton index in the heart and lung of PAH rats. In vitro, TMP can regulate the levels of smooth muscle protein 22‐alpha (SM22‐α), and myocardin as well as intracellular cytokines such as NO, transforming growth factor beta (TGF‐β), and connective tissue growth factor (CTGF) in a dose‐dependent manner (25, 50, or 100 μM). Transfection of myocardin small interfering RNA (siRNA) aggravated the proliferation of pulmonary artery smooth muscle cells (PSMCs), and the regulatory effect of TMP on α‐smooth muscle actin (α‐SMA) and osteopontin (OPN) disappeared. The application of 10 nM estrogen receptor alpha (ERα) inhibitor MPP promoted the proliferation of PSMCs, but it does not affect the inhibition of TMP on PSMCs proliferation. Finally, we found that TMP promoted the nucleation of myocardin‐related transcription factor‐A (MRTF‐A) and combined it with myocardin. In conclusion, TMP can inhibit the transformation of PSMCs from the contractile phenotype to the proliferative phenotype by promoting the formation of the nuclear (MRTF‐A/myocardin) transcription complex to treat PAH.

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Selexipag for the treatment of pulmonary arterial hypertension

Cited by 11 publications

References 17 publications

The Role of Sex in the Pathophysiology of Pulmonary Hypertension

The Role of Sex in the Pathophysiology of Pulmonary Hypertension

Nivolumab-Induced Impressive Response of Refractory Pulmonary Sarcomatoid Carcinoma with Brain Metastasis

Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells

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