The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series)
Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the “serotonin h...
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| Format: | Article |
| Language: | English |
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Wiley
2018-02-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894018759125 |
| _version_ | 1811228344608358400 |
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| author | Margaret (Mandy) R. MacLean |
| author_facet | Margaret (Mandy) R. MacLean |
| author_sort | Margaret (Mandy) R. MacLean |
| collection | DOAJ |
| description | Increased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the “serotonin hypothesis of pulmonary hypertension.” Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1 (TPH1) is increased in patients with PAH and serotonin can act in a paracrine fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans, serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5-HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC contraction and proliferation via activation of downstream proliferative and contractile signaling pathways. Here we will review the current status of the serotonin hypothesis and discuss potential and novel therapeutic targets. |
| first_indexed | 2024-04-12T09:57:27Z |
| format | Article |
| id | doaj.art-62b7a499dcb74926857ebe39981eb042 |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-04-12T09:57:27Z |
| publishDate | 2018-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-62b7a499dcb74926857ebe39981eb0422022-12-22T03:37:39ZengWileyPulmonary Circulation2045-89402018-02-01810.1177/2045894018759125The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series)Margaret (Mandy) R. MacLeanIncreased synthesis of serotonin and/or activity of serotonin in pulmonary arteries has been implicated in the pathobiology of pulmonary arterial hypertension (PAH). The incidence of PAH associated with diet pills such as aminorex, fenfluramine, and chlorphentermine initially led to the “serotonin hypothesis of pulmonary hypertension.” Over the last couple of decades there has been an accumulation of convincing evidence that targeting serotonin synthesis or signaling is a novel and promising approach to the development of novel therapies for PAH. Pulmonary endothelial serotonin synthesis via tryptophan hydroxlase 1 (TPH1) is increased in patients with PAH and serotonin can act in a paracrine fashion on underlying pulmonary arterial smooth muscle cells (PASMCs), In humans, serotonin can enter PASMCs via the serotonin transporter (SERT) or activate the 5-HT1B receptor; 5-HT1B activation and SERT activity cooperate to induce PASMC contraction and proliferation via activation of downstream proliferative and contractile signaling pathways. Here we will review the current status of the serotonin hypothesis and discuss potential and novel therapeutic targets.https://doi.org/10.1177/2045894018759125 |
| spellingShingle | Margaret (Mandy) R. MacLean The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) Pulmonary Circulation |
| title | The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) |
| title_full | The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) |
| title_fullStr | The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) |
| title_full_unstemmed | The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) |
| title_short | The serotonin hypothesis in pulmonary hypertension revisited: targets for novel therapies (2017 Grover Conference Series) |
| title_sort | serotonin hypothesis in pulmonary hypertension revisited targets for novel therapies 2017 grover conference series |
| url | https://doi.org/10.1177/2045894018759125 |
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