The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension
Abstract
:1. Introduction
2. Pathophysiology of PH
3. Pulmonary Vascular Remodeling in PH
4. Prostaglandins and PH
5. Role of PGE2 Receptors in PH
5.1. Role of EP1 in PH
5.2. Role of EP2 in PH
5.3. Role of EP3 in PH
5.4. Role of EP4 in PH
6. Conclusions and Prospects
Author Contributions
Funding
Conflicts of Interest
References
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Three Classic Drugs for the Treatment of PH | Classification | Drug Name | Administration Method | Target | Therapeutic Features | Advantages | Disadvantages | Preference |
---|---|---|---|---|---|---|---|---|
1 | PGI2 analogues | Epoprostenol | Intravenous | IP | Slow, incremental and individualized dosing where the patient is closely monitored for tolerability. In most case, PGI2 analogues are reserved for patients with severe PH. | Exercise tolerance, hemodynamics, long-term survival and mortality of patients with PH has improved. | The half-life at room temperature is very short, requiring permanent intravenous catheter continuous infusion, causing infection and pain at the site of injection. It is complicated, uncomfortable for patients, and very costly. Common side effects: systemic hypotension, flushing, jaw pain and nausea. Its serious side effects: catheter associated sepsis. | Preferred drug; In North America and in some European countries since the mid-1990s |
Treprostinil | Subcutaneous, intravenous, inhalation and oral | A stable PGI2 analogue; Indexes of dyspnea, signs, symptoms and exercise capacity of PH, and hemodynamic measures significantly improve. | Causing infection and pain at the site of injection. Common side effects: systemic hypotension, flushing, jaw pain and nausea. | Alternative drug; In the United States since 2002 | ||||
Iloprost | Inhalation | A chemically stable PGI2 analogue; Hemodynamic values were significantly improved. | Its relatively short duration of action; It must be inhaled as many as 6 to 12 times a day; Side effects included cough and symptoms linked to systemic vasodilatation; It makes patients with PH have a higher rate of syncope. | In Japan | ||||
Beraprost | Oral | The first biologically stable and orally PGI2 analogue which is absorbed rapidly; The peak concentration was reached 30 minutes after oral administration; With a half-life of 35–40 min. | There was no significant change in cardiovascular hemodynamics. | For treating primary PH in Europe. | ||||
IP selective agonist | Selexipag | Oral | Specific for IP, it has little or no effect on other prostanoid receptors; The risk of the primary composite end point of death or a complication related to PAH was significantly improved. | Side effects: headache, diarrhea, systemic hypotension, flushing, jaw pain and nausea. | ||||
2 | Endothelin receptor antagonists | Bosentan | Oral | ETAR and ETBR | 125 mg/bid Monthly monitoring of liver function tests is mandatory. | Significant improvements in PAP, cardiac output, and PVR | Development of abnormal hepatic function; It is contraindicated during pregnancy because of its teratogenic potential; Its long-term requires further evaluation. | For the treatment of PAH in North America in 2001 and in Europe in 2002. |
3 | Phosphodiesterase inhibitors | Sildenafil | Oral | PDE5 | long-term adjunctive treatment can improve exercise capacity and pulmonary hemodynamics. | The experience with sildenafil is preliminary, and controlled studies are in progress to determine its efficacy, side effects, and safety. |
PGI2 Analogues | IP | EP1 | EP2 | EP3 | EP4 | |
---|---|---|---|---|---|---|
Iloprost | Human | 4 | 1 | 1172 | 203 | 212 |
Mouse | 11 | 21 | 1600 | 27 | 2300 | |
Treprostinil | Human | 32 | 212 | 3.6 | 2505 | 826 |
Mouse | YES | ND | YES | ND | ND | |
Beraprost | Human | 39 | 680 | |||
Mouse | 16 | 110 | ||||
Cicaprost | Human | 17 | >1340 | >1340 | 255 | 44 |
Mouse | 10 | 1300 | 170 |
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Ye, L.; Wang, B.; Xu, H.; Zhang, X. The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension. Metabolites 2023, 13, 1152. https://doi.org/10.3390/metabo13111152
Ye L, Wang B, Xu H, Zhang X. The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension. Metabolites. 2023; 13(11):1152. https://doi.org/10.3390/metabo13111152
Chicago/Turabian StyleYe, Lan, Bing Wang, Hu Xu, and Xiaoyan Zhang. 2023. "The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension" Metabolites 13, no. 11: 1152. https://doi.org/10.3390/metabo13111152